Abstract
In recent years, the incidence of colorectal cancer (CRC) and breast cancer (BC) has increased worldwide and caused a higher mortality rate due to the lack of selective anti-tumor therapies. Current chemotherapies and surgical interventions are significantly preferred modalities to treat CRC or BC in advanced stages but the prognosis for patients with advanced CRC and BC remains dismal. The immunotherapy technique of chimeric antigen receptor (CAR)-T cells has resulted in significant clinical outcomes when treating hematologic malignancies. The novel CAR-T therapy target antigens include GUCY2C, CLEC14A, CD26, TEM8/ANTXR1, PDPN, PTK7, PODXL, CD44, CD19, CD20, CD22, BCMA, GD2, Mesothelin, TAG-72, CEA, EGFR, B7H3, HER2, IL13Ra2, MUC1, EpCAM, PSMA, PSCA, NKG2D. The significant aim of this review is to explore the recently updated information pertinent to several novel targets of CAR-T for CRC, and BC. We vividly described the challenges of CAR-T therapies when treating CRC or BC. The immunosuppressive microenvironment of solid tumors, the shortage of tumor-specific antigens, and post-treatment side effects are the major hindrances to promoting the development of CAR-T cells. Several clinical trials related to CAR-T immunotherapy against CRC or BC have already been in progress. This review benefits academicians, clinicians, and clinical oncologists to explore more about the novel CAR-T targets and overcome the challenges during this therapy.
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References
Ahn JC, Teng PC, Chen PJ et al (2021) Detection of circulating tumor cells and their implications as a biomarker for diagnosis, prognostication, and therapeutic monitoring in hepatocellular carcinoma. Hepatology 73:422–436. https://doi.org/10.1002/hep.31165
Amatya C, Pegues MA, Lam N et al (2021) Development of CAR T cells expressing a suicide gene plus a chimeric antigen receptor targeting signaling lymphocytic-activation molecule F7. Mol Ther 29:702–717. https://doi.org/10.1016/j.ymthe.2020.10.008
Aoe T, Goto S, Ohno H et al (1994) Different cytoplasmic structure of the CD3ζ family dimer modulates the activation signal and function of T cells. Int Immunol 6:1671–1679. https://doi.org/10.1093/intimm/6.11.1671
Baybutt T, Snook A, Waldman S et al (2020) 105 A third-generation human GUCY2C-targeted CAR-T cell for colorectal cancer immunotherapy. J Immunother Cancer 8(Suppl 3):A116–A116. https://doi.org/10.1136/jitc-2020-SITC2020.0105
Boice M, Salloum D, Mourcin F et al (2016) Loss of the HVEM tumor suppressor in lymphoma and restoration by modified CAR-T cells. Cell 167:405–418. https://doi.org/10.1016/j.cell.2016.08.032
Bridgeman JS, Hawkins RE, Bagley S et al (2010) The optimal antigen response of chimeric antigen receptors harboring the CD3ζ transmembrane domain is dependent upon incorporation of the receptor into the endogenous TCR/CD3 complex. J Immunol 184:6938–6949. https://doi.org/10.4049/jimmunol.0901766
Brown TC, Sankpal NV, Gillanders WE (2021) Functional implications of the dynamic regulation of EpCAM during epithelial-to-mesenchymal transition. Biomolecules 11:956. https://doi.org/10.3390/biom11070956
Budi HS, Ahmad FN, Achmad H et al (2022) Human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor (CAR) for tumor immunotherapy; recent progress. Stem Cell Res Ther 13:1–21. https://doi.org/10.1186/s13287-022-02719-0
Burga RA, Thorn M, Point GR et al (2015) Liver myeloid-derived suppressor cells expand in response to liver metastases in mice and inhibit the anti-tumor efficacy of anti-CEA CAR-T. Cancer Immunol Immunother 64:817–829. https://doi.org/10.1007/s00262-015-1692-6
Carney WP, Leitzel K, Ali S et al (2007) HER-2 therapy. HER-2/neu diagnostics in breast cancer. Breast Cancer Res 9:207. https://doi.org/10.1186/bcr1664
Cerrano M, Ruella M, Perales MA et al (2020) The advent of CAR T-cell therapy for lymphoproliferative neoplasms: integrating research into clinical practice. Front Immunol 11:888. https://doi.org/10.3389/fimmu.2020.00888
Cha SE, Kujawski M, Yazaki PJ et al (2021) Tumor regression and immunity in combination therapy with anti-CEA chimeric antigen receptor T cells and anti-CEA-IL2 immunocytokine. Oncoimmunology 10:1899469. https://doi.org/10.1080/2162402X.2021.1899469
Chen N, Morello A, Tano Z et al (2017) CAR T-cell intrinsic PD-1 checkpoint blockade: a two-in-one approach for solid tumor immunotherapy. Oncoimmunology 6:e1273302. https://doi.org/10.1080/2162402X.2016.1273302
Chmielewski M, Abken H (2015) TRUCKs: the fourth generation of CARs. Expert Opin Biol Ther 15:1145–1154. https://doi.org/10.1517/14712598.2015.1046430
Cho J, Kim KM, Kim HC et al (2019) The prognostic role of tumor associated glycoprotein 72 (TAG-72) in stage II and III colorectal adenocarcinoma. Pathol Res Pract 215:171–176. https://doi.org/10.1016/j.prp.2018.10.024
Corti C, Venetis K, Sajjadi E et al (2022) CAR-T cell therapy for triple-negative breast cancer and other solid tumors: preclinical and clinical progress. Expert Opin Investig Drugs 31:593–605. https://doi.org/10.1080/13543784.2022.2054326
Cruz-Duarte R, Rebelo de Almeida C, Negrão M et al (2022) Predictive and therapeutic implications of a novel PLCγ1/SHP2-driven mechanism of cetuximab resistance in metastatic colorectal cancerPLCγ1: clinical implications for cetuximab therapy. Clin Cancer Res 28:1203–1216. https://doi.org/10.1158/1078-0432.CCR-21-1992
D’Aloia MM, Zizzari IG, Sacchetti B et al (2018) CAR-T cells: the long and winding road to solid tumors. Cell Death Dis 9:282. https://doi.org/10.1038/s41419-018-0278-6
Donnadieu E, Dupré L, Pinho LG et al (2020) Surmounting the obstacles that impede effective CAR T cell trafficking to solid tumors. J Leukoc Biol 108:1067–1079. https://doi.org/10.1002/JLB.1MR0520-746R
Drago JZ, Ferraro E, Abuhadra N et al (2022) Beyond HER2: targeting the ErbB receptor family in breast cancer. Cancer Treat Rev 109:102436. https://doi.org/10.1016/j.ctrv.2022.102436
Fakih MG, Padmanabhan A (2006) CEA monitoring in colorectal cancer. What you should know. Oncology 20:579–587. https://europepmc.org/article/med/16773844
Fan J, Das JK, Xiong X et al (2021) Development of CAR-T cell persistence in adoptive immunotherapy of solid tumors. Front Oncol 10:574860. https://doi.org/10.3389/fonc.2020.574860
Faust JR, Hamill D, Kolb EA et al (2022) Mesothelin: An immunotherapeutic target beyond solid tumors. Cancers 14:1550. https://doi.org/10.3390/cancers14061550
Fesnak AD, June VH, Levine BL (2016) Engineered T cells: the promise and challenges of cancer immunotherapy. Nat Rev Cancer 16:566–581. https://doi.org/10.1038/nrc.2016.97
Fong D, Moser P, Kasal A et al (2014) Loss of membranous expression of the intracellular domain of Ep CAM is a frequent event and predicts poor survival in patients with pancreatic cancer. Histopathology 64:683–692. https://doi.org/10.1111/his.12307
Fournier C, Martin F, Zitvogel L et al (2017) Trial watch: adoptively transferred cells for anticancer immunotherapy. Oncoimmunology 6:e1363139. https://doi.org/10.1080/2162402X.2017.1363139
Freed DM, Bessman NJ, Kiyatkin A et al (2017) EGFR ligands differentially stabilize receptor dimers to specify signaling kinetics. Cell 171:683–695. https://doi.org/10.1016/j.cell.2017.09.017
Gay F, D’Agostino M, Giaccone L et al (2017) Immuno-oncologic approaches: CAR-T cells and checkpoint inhibitors. Clin Lymphoma Myeloma Leuk 17:471–478. https://doi.org/10.1016/j.clml.2017.06.014
Ghazi B, El Ghanmi A, Kandoussi S et al (2022) CAR T-cells for colorectal cancer immunotherapy: ready to go? Front Immunol 13:978195. https://doi.org/10.3389/fimmu.2022.978195
Globerson-Levin A, Waks T, Eshhar Z (2014) Elimination of progressive mammary cancer by repeated administrations of chimeric antigen receptor-modified T cells. Mol Ther 22:1029–1038. https://doi.org/10.1038/mt.2014.28
Golubovskaya VM, Berahovich R, Zhou H et al (2020) PLAP (placental alkaline phosphatase)-CAR-T cells specifically target colorectal cancer. Cancer Res 80(16_Suppl):4228–4228. https://doi.org/10.1158/1538-7445.AM2020-4228
Guedan S, Posey AD Jr, Shaw C et al (2018) Enhancing CAR T cell persistence through ICOS and 4-1BB costimulation. JCI Insight 3:e96976. https://doi.org/10.1172/jci.insight.96976
Guedan S, Calderon H, Posey AD Jr et al (2019) Engineering and design of chimeric antigen receptors. Mol Ther Methods Clin Dev 12:145–156. https://doi.org/10.1016/j.omtm.2018.12.009
Guizhen Z, Guanchang J, Liwen L et al (2022) The tumor microenvironment of hepatocellular carcinoma and its targeting strategy by CAR-T cell immunotherapy. Front Endocrinol 13:918869. https://doi.org/10.3389/fendo.2022.918869
Hagemann UB, Ellingsen C, Schuhmacher J et al (2019) Mesothelin-targeted thorium-227 conjugate (MSLN-TTC): Preclinical evaluation of a new targeted alpha therapy for mesothelin-positive cancers MSLN-targeted thorium-227 conjugate. Clin Cancer Res 25:4723–4734. https://doi.org/10.1158/1078-0432.CCR-18-3476
Hauck W, Stanners CP (1991) Control of carcinoembryonic antigen gene family expression in a differentiating colon carcinoma cell line, Caco-2. Cancer Res 51:3526–3533 (51/13/3526/2443891/cr0510133526)
He Y, Wang X (2020) Identification of molecular features correlating with tumor immunity in gastric cancer by multi-omics data analysis. Ann Transl Med 8:1050. https://doi.org/10.21037/atm-20-922
Hege KM, Bergsland EK, Fisher GA et al (2017) Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer. J Immunother Cancer 5:22. https://doi.org/10.1186/s40425-017-0222-9
Holzinger A, Abken H (2017) CAR T cells targeting solid tumors: carcinoembryonic antigen (CEA) proves to be a safe target. Cancer Immunol Immunother 66:1505–1507. https://doi.org/10.1007/s00262-017-2045-4
Hombach AA, Rappl G, Abken H (2019) Blocking CD30 on T cells by a dual specific CAR for CD30 and colon cancer antigens improves the CAR T cell response against CD30− tumors. Mol Ther 27:1825–1835. https://doi.org/10.1016/j.ymthe.2019.06.007
Hou X, Wang F, Meng X et al (2022) Construction of a 124I-labeled specific antibody for the noninvasive detection of mesothelin-overexpressing tumors. Mol Pharm 19:3623–3631. https://doi.org/10.1021/acs.molpharmaceut.2c00342
Hsu HJ, Tung CP, Yu CM et al (2021) Eradicating mesothelin-positive human gastric and pancreatic tumors in xenograft models with optimized anti-mesothelin antibody–drug conjugates from synthetic antibody libraries. Sci Rep 11:15430. https://doi.org/10.1038/s41598-021-94902-1
Hu B, Zou Y, Zhang L et al (2019) Nucleofection with plasmid DNA for CRISPR/Cas9-mediated inactivation of programmed cell death protein 1 in CD133-specific CAR T cells. Hum Gene Ther 30:446–458. https://doi.org/10.1089/hum.2017.234
Huang R, Li X, He Y et al (2020a) Recent advances in CAR-T cell engineering. J Hematol Oncol 13:86. https://doi.org/10.1186/s13045-020-00910-5
Huang Y, Li D, Zhang PF et al (2020b) IL-18R-dependent and independent pathways account for IL-18-enhanced antitumor ability of CAR-T cells. FASEB J 34:1768–1782. https://doi.org/10.1096/fj.201901809R
Hudecek M, Sommermeyer D, Kosasih PL et al (2015) The nonsignaling extracellular spacer domain of chimeric antigen receptors is decisive for in vivo antitumor activity. Cancer Immunol Res 3:125–135. https://doi.org/10.1158/2326-6066.CIR-14-0127
Hwu P, Shafer G, Treisman J et al (1993) Lysis of ovarian cancer cells by human lymphocytes redirected with a chimeric gene composed of an antibody variable region and the Fc receptor gamma chain. J Exp Med 178:361–366. https://doi.org/10.1084/jem.178.1.361
Hwu P, Yang J, Cowherd R et al (1995) In vivo antitumor activity of T cells redirected with chimeric antibody/T-cell receptor genes. Cancer Res 55:3369–3373 (55/15/3369/2457347/cr0550153369)
Hyrenius-Wittsten A, Su Y, Park M et al (2021) SynNotch CAR circuits enhance solid tumor recognition and promote persistent antitumor activity in mouse models. Sci Transl Med 13:eabd8836. https://doi.org/10.1126/scitranslmed.abd8836
John LB, Devaud C, Duong CP et al (2013) Anti-PD-1 antibody therapy potently enhances the eradication of established tumors by gene-modified T cells anti-PD-1 therapy enhances tumor rejection by CAR T cells. Clin Cancer Res 19:5636–5646. https://doi.org/10.1158/1078-0432.CCR-13-0458
Jones S, Rappoport JZ (2014) Interdependent epidermal growth factor receptor signalling and trafficking. Int J Biochem Cell Biol 51:23–28. https://doi.org/10.1016/j.biocel.2014.03.014
June CH, O’Connor RS, Kawalekar OU et al (2018) CAR T cell immunotherapy for human cancer. Science 359:1361–1365. https://doi.org/10.1126/science.aar6711
Kagoya Y, Tanaka S, Guo T et al (2018) A novel chimeric antigen receptor containing a JAK–STAT signaling domain mediates superior antitumor effects. Nat Med 24:352–359. https://doi.org/10.1038/nm.4478
Katz SC, Burga RA, McCormack E et al (2015) Phase I hepatic immunotherapy for metastases study of intra-arterial chimeric antigen receptor–modified T-cell therapy for CEA+ liver metastases hepatic artery CAR-T infusions. Clin Cancer Res 21:3149–3159. https://doi.org/10.1158/1078-0432.CCR-14-1421
Katz SC, Hardaway J, Prince E et al (2020) HITM-SIR: phase Ib trial of intraarterial chimeric antigen receptor T-cell therapy and selective internal radiation therapy for CEA+ liver metastases. Cancer Gene Ther 27:341–355. https://doi.org/10.1038/s41417-019-0104-z
Keshavarz A, Salehi A, Khosravi S et al (2022) Recent findings on chimeric antigen receptor (CAR)-engineered immune cell therapy in solid tumors and hematological malignancies. Stem Cell Res Ther 13:482. https://doi.org/10.1186/s13287-022-03163-w
Knödler M, Körfer J, Kunzmann V et al (2018) Randomised phase II trial to investigate catumaxomab (anti-EpCAM× anti-CD3) for treatment of peritoneal carcinomatosis in patients with gastric cancer. Br J Cancer 119:296–302. https://doi.org/10.1038/s41416-018-0150-6
Kotch C, Barrett D, Teachey DT (2019) Tocilizumab for the treatment of chimeric antigen receptor T cell-induced cytokine release syndrome. Expert Rev Clin Immunol 15:813–822. https://doi.org/10.1080/1744666X.2019.1629904
Kozani PS, Kozani PS, Rahbarizadeh F (2021) Novel antigens of CAR T cell therapy: new roads; old destination. Transl Oncol 14:101079. https://doi.org/10.1016/j.tranon.2021.101079
Kremer V, Ligtenberg MA, Zendehdel R et al (2017) Genetic engineering of human NK cells to express CXCR2 improves migration to renal cell carcinoma. J Immunother Cancer 5:73. https://doi.org/10.1186/s40425-017-0275-9
Kumar V, Abbas AK, Aster JC (2017) Robbins basic pathology e-book. Elsevier, New York. https://doi.org/10.1093/ajcp/aqx095
Lech G, Słotwiński R, Słodkowski M et al (2016) Colorectal cancer tumour markers and biomarkers: recent therapeutic advances. World J Gastroenterol 22:1745. https://doi.org/10.3748/wjg.v22.i5.1745
Levitsky K, Li Z, Pham MT et al (2020) Allogeneic anti-PTK7 CAR-T cells for the treatment of solid tumors. Cancer Res 80(16_Suppl):3243–3243. https://doi.org/10.1158/1538-7445.AM2020-3243
Li J, Han X, Yu X et al (2018) Clinical applications of liquid biopsy as prognostic and predictive biomarkers in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA. J Exp Clin Cancer Res 37:213. https://doi.org/10.1186/s13046-018-0893-1
Li X, Berahovich R, Zhou H et al (2020a) PLAP-CAR T cells mediate high specific cytotoxicity against colon cancer cells. Front Biosci 25:1765–1786. https://doi.org/10.2741/4877
Li Y, Xiao F, Zhang A et al (2020b) Oncolytic adenovirus targeting TGF-β enhances anti-tumor responses of mesothelin-targeted chimeric antigen receptor T cell therapy against breast cancer. Cell Immunol 348:104041. https://doi.org/10.1016/j.cellimm.2020.104041
Li Z, Chi Z, Ang WX et al (2020c) Experimental treatment of colorectal cancer in mice with human T cells electroporated with NKG2D RNA CAR. Immunotherapy 12:733–748. https://doi.org/10.2217/imt-2019-0137
Liao MY, Lai JK, Kuo MYP et al (2015) An anti-EpCAM antibody EpAb2-6 for the treatment of colon cancer. Oncotarget 6:24947. https://doi.org/10.18632/oncotarget.4453
Lim WA, June CH (2017) The principles of engineering immune cells to treat cancer. Cell 168:724–740. https://doi.org/10.1016/j.cell.2017.01.016
Lipowska-Bhalla G, Gilham DE, Hawkins RE et al (2012) Targeted immunotherapy of cancer with CAR T cells: achievements and challenges. Cancer Immunol Immunother 61:953–962. https://doi.org/10.1007/s00262-012-1254-0
Liu B, Yan L, Zhou M (2019) Target selection of CAR T cell therapy in accordance with the TME for solid tumors. Am J Cancer Res 9:228 (ajcr0090440)
Liu G, Rui W, Zheng H et al (2020) CXCR2-modified CAR-T cells have enhanced trafficking ability that improves treatment of hepatocellular carcinoma. Eur J Immunol 50:712–724. https://doi.org/10.1002/eji.201948457
Liu G, Zhang Q, Li D et al (2021a) PD-1 silencing improves anti-tumor activities of human mesothelin-targeted CAR T cells. Hum Immunol 82:130–138. https://doi.org/10.1016/j.humimm.2020.12.002
Liu G, Zhang Q, Liu G et al (2021b) Disruption of adenosine 2A receptor improves the anti-tumor function of anti-mesothelin CAR T cells both in vitro and in vivo. Exp Cell Res 409:112886. https://doi.org/10.1016/j.yexcr.2021.112886
Lloyd A, Vickery ON, Laugel B (2013) Beyond the antigen receptor: editing the genome of T-cells for cancer adoptive cellular therapies. Front Immunol 4:221. https://doi.org/10.3389/fimmu.2013.00221
Lu J, Jiang G (2022) The journey of CAR-T therapy in hematological malignancies. Mol Cancer 21:194. https://doi.org/10.1186/s12943-022-01663-0
Ma X, Shou P, Smith C et al (2020) Interleukin-23 engineering improves CAR T cell function in solid tumors. Nat Biotechnol 38:448–459. https://doi.org/10.1038/s41587-019-0398-2
Magee MS, Kraft CL, Abraham TS et al (2016) GUCY2C-directed CAR-T cells oppose colorectal cancer metastases without autoimmunity. Oncoimmunology 5:e1227897. https://doi.org/10.1080/2162402X.2016.1227897
Magee MS, Abraham TS, Baybutt TR et al (2018) Human GUCY2C-targeted chimeric antigen receptor (CAR)-expressing T cells eliminate colorectal cancer metastases CAR-T cells target human GUCY2C+ colorectal tumors. Cancer Immunol Res 6:509–516. https://doi.org/10.1158/2326-6066.CIR-16-0362
Majzner RG, Ramakrishna S, Yeom KW et al (2022) GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas. Nature 603:934–941. https://doi.org/10.1038/s41586-022-04489-4
Marei HE, Althani A, Caceci T et al (2019) Recent perspective on CAR and Fcγ-CR T cell immunotherapy for cancers: preclinical evidence versus clinical outcomes. Biochem Pharmacol 166:335–346. https://doi.org/10.1016/j.bcp.2019.06.002
Martinez M, Moon EK (2019) CAR T cells for solid tumors: new strategies for finding, infiltrating, and surviving in the tumor microenvironment. Front Immunol 10:128. https://doi.org/10.3389/fimmu.2019.00128
Martínez-Lago N, Chucla TC, De Castro BA et al (2022) Efficacy, safety and prognostic factors in patients with refractory metastatic colorectal cancer treated with trifluridine/tipiracil plus bevacizumab in a real-world setting. Sci Rep 12:14612. https://doi.org/10.1038/s41598-022-18871-9
Masoumi E, Jafarzadeh L, Mirzaei HR et al (2020) Genetic and pharmacological targeting of A2a receptor improves function of anti-mesothelin CAR T cells. J Exp Clin Cancer Res 39:49. https://doi.org/10.1186/s13046-020-01546-6
McGowan E, Lin Q, Ma G et al (2020) PD-1 disrupted CAR-T cells in the treatment of solid tumors: promises and challenges. Biomed Pharmacother 121:109625. https://doi.org/10.1016/j.biopha.2019.109625
Minnix M, Li L, Yazaki P et al (2020) Improved targeting of an anti-TAG-72 antibody drug conjugate for the treatment of ovarian cancer. Cancer Med 9:4756–4767. https://doi.org/10.1002/cam4.3078
Mishra V, Bose A, Kiran S et al (2021) Gut-associated cGMP mediates colitis and dysbiosis in a mouse model of an activating mutation in GUCY2C. J Exp Med 218:e2021047. https://doi.org/10.1084/jem.20210479
Moasser MM (2007) The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene 26:6469–6487. https://doi.org/10.1038/sj.onc.1210477
Moghimi B, Muthugounder S, Jambon S et al (2021) Preclinical assessment of the efficacy and specificity of GD2-B7H3 SynNotch CAR-T in metastatic neuroblastoma. Nat Commun 12:511. https://doi.org/10.1038/s41467-020-20785-x
Moon DH, Lindsay DP, Hong S et al (2018) Clinical indications for, and the future of, circulating tumor cells. Adv Drug Deliv Rev 125:143–150. https://doi.org/10.1016/j.addr.2018.04.002
Morgan RA, Yang JC, Kitano M et al (2010) Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther 18:843–851. https://doi.org/10.1038/mt.2010.24
Mount CW, Majzner RG, Sundaresh S et al (2018) Potent antitumor efficacy of anti-GD2 CAR T cells in H3-K27M+ diffuse midline gliomas. Nat Med 24:572–579. https://doi.org/10.1038/s41591-018-0006-x
Mullard A (2021) FDA approves first BCMA-targeted CAR-T cell therapy. Nat Rev Drug Discov 20:332. https://doi.org/10.1038/d41573-021-00063-1
Munshi NC, Anderson LD Jr, Shah N et al (2021) Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med 384:705–716. https://doi.org/10.1056/NEJMoa2024850
Nalawade SA, Shafer P, Bajgain P et al (2021) Selectively targeting myeloid-derived suppressor cells through TRAIL receptor 2 to enhance the efficacy of CAR T cell therapy for treatment of breast cancer. J Immunother Cancer 9:e003237. https://doi.org/10.1136/jitc-2021-003237
Nasiri F, Kazemi M, Mirarefin SMJ et al (2022) CAR-T cell therapy in triple-negative breast cancer: hunting the invisible devil. Front Immunol 13:1018786. https://doi.org/10.3389/fimmu.2022.1018786
Nathanson DR, Culliford AT IV, Shia J et al (2003) HER 2/neu expression and gene amplification in colon cancer. Int J Cancer 105:796–802. https://doi.org/10.1002/ijc.11137
Neelapu SS (2019) Managing the toxicities of car T-cell therapy. Hematol Oncol 37:48–52. https://doi.org/10.1002/hon.2595
Newick K, Moon E, Albelda SM (2016) Chimeric antigen receptor T-cell therapy for solid tumors. Mol Ther Oncolytics 3:16006. https://doi.org/10.1038/mto.2016.6
Newick K, O’Brien S, Moon E et al (2017) CAR T cell therapy for solid tumors. Annu Rev Med 68:139–152. https://doi.org/10.1146/annurev-med-062315-120245
Nishimoto N, Terao K, Mima T et al (2008) Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti–IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood 112:3959–3964. https://doi.org/10.1182/blood-2008-05-155846
Niv Y (2008) MUC1 and colorectal cancer pathophysiology considerations. World J Gastroenterol 14:2139. https://doi.org/10.3748/wjg.14.2139
Orning P, Lien E, Fitzgerald KA (2019) Gasdermins and their role in immunity and inflammation. J Exp Med 216:2453–2465. https://doi.org/10.1084/jem.20190545
Ouyang M, Wu W, Zou Y et al (2010) Immunoreactivity and prognostic value of tumor-associated glycoprotein 72 in primary gallbladder carcinoma. Surg Oncol 19:82–87. https://doi.org/10.1016/j.suronc.2009.03.010
Oved JH, Barrett DM, Teachey DT (2019) Cellular therapy: immune-related complications. Immunol Rev 290:114–126. https://doi.org/10.1111/imr.12768
Owen K, Ghaly R, Shohdy KS et al (2022) Lymphodepleting chemotherapy practices and effect on safety and efficacy outcomes in patients with solid tumours undergoing T cell receptor-engineered T cell (TCR-T) Therapy: a systematic review and meta-analysis. Cancer Immunol Immunother 72:805–814. https://doi.org/10.1007/s00262-022-03287-1
Patel JM, Dale GA, Vartabedian VF et al (2014) Cancer CARtography: charting out a new approach to cancer immunotherapy. Immunotherapy 6:675–678. https://doi.org/10.2217/imt.14.44
Patriarca C, Macchi RM, Marschner AK et al (2012) Epithelial cell adhesion molecule expression (CD326) in cancer: a short review. Cancer Treat Rev 38:68–75. https://doi.org/10.1016/j.ctrv.2011.04.002
Pattison AM, Merlino DJ, Blomain ES et al (2016) Guanylyl cyclase C signaling axis and colon cancer prevention. World J Gastroenterol 22:8070. https://doi.org/10.3748/wjg.v22.i36.8070
Pehlivan KC, Duncan BB, Lee DW (2018) CAR-T cell therapy for acute lymphoblastic leukemia: transforming the treatment of relapsed and refractory disease. Curr Hematol Malignancy Rep 13:396–406. https://doi.org/10.1007/s11899-018-0470-x
Peterse EF, Meester RG, Siegel RL et al (2018) The impact of the rising colorectal cancer incidence in young adults on the optimal age to start screening: microsimulation analysis I to inform the American Cancer Society colorectal cancer screening guideline. Cancer 124:2964–2973. https://doi.org/10.1002/cncr.31543
Pfeifer R (2018) Evaluation of SSEA-4 as a CAR T cell therapeutic target for the treatment of chemoresistant triple negative breast cancers. Universität Tübingen, Tübingen. https://doi.org/10.15496/publikation-26519
Prasad V (2018) Tisagenlecleucel—the first approved CAR-T-cell therapy: implications for payers and policy makers. Nat Rev Clin Oncol 15:11–12. https://doi.org/10.1038/nrclinonc.2017.156
Qin X, Wu F, Chen C et al (2022) Recent advances in CAR-T cells therapy for colorectal cancer. Front Immunol 13:904137. https://doi.org/10.3389/fimmu.2022.904137
Qu C, Zhang H, Cao H et al (2022) Tumor buster—where will the CAR-T cell therapy ‘missile’ go? Mol Cancer 21:201. https://doi.org/10.1186/s12943-022-01669-8
Rahbarizadeh F, Ahmadvand D, Moghimi S (2019) CAR T-cell bioengineering: single variable domain of heavy chain antibody targeted CARs. Adv Drug Deliv Rev 141:41–46. https://doi.org/10.1016/j.addr.2019.04.006
Rizeq B, Zakaria Z, Ouhtit A (2018) Towards understanding the mechanisms of actions of carcinoembryonic antigen-related cell adhesion molecule 6 in cancer progression. Cancer Sci 109:33–42. https://doi.org/10.1111/cas.13437
Rupp LJ, Schumann K, Roybal KT et al (2017) CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells. Sci Rep 7:737. https://doi.org/10.4049/jimmunol.196.Supp.214.24
Sachdev J, Maitland M, Sharma M et al (2016) A phase 1 study of PF-06647020, an antibody-drug conjugate (ADC) targeting protein tyrosine kinase 7 (PTK7), in patients with advanced solid tumors including platinum resistant ovarian cancer (OVCA). Ann Oncol 27:vi570. https://doi.org/10.1093/annonc/mdw435.29
Sadelain M, Rivière I, Brentjens R (2003) Targeting tumours with genetically enhanced T lymphocytes. Nat Rev Cancer 3:35–45. https://doi.org/10.1038/nrc971
Sahm C, Schönfeld K, Wels WS (2012) Expression of IL-15 in NK cells results in rapid enrichment and selective cytotoxicity of gene-modified effectors that carry a tumor-specific antigen receptor. Cancer Immunol Immunother 61:1451–1461. https://doi.org/10.1007/s00262-012-1212-x
Schepisi G, Gianni C, Palleschi M et al (2023) The new frontier of immunotherapy: chimeric antigen receptor T (CAR-T) cell and macrophage (CAR-M) therapy against breast cancer. Cancers 15:1597. https://doi.org/10.3390/cancers15051597
Schmidts A, Maus MV (2018) Making CAR T cells a solid option for solid tumors. Front Immunol 9:2593. https://doi.org/10.3389/fimmu.2018.02593
Schubert ML, Schmitt M, Wang L et al (2021) Side-effect management of chimeric antigen receptor (CAR) T-cell therapy. Ann Oncol 32:34–48. https://doi.org/10.1016/j.annonc.2020.10.478
Seeber A, Untergasser G, Spizzo G et al (2016) Predominant expression of truncated EpCAM is associated with a more aggressive phenotype and predicts poor overall survival in colorectal cancer. Int J Cancer 139:657–663. https://doi.org/10.1002/ijc.30099
Sertesen E, Yekedüz E, Köksoy EB et al (2022) The effect of primary tumour resection on patients with synchronous metastatic colorectal cancer treated with cetuximab containing regimens. ANZ J Surg 93:945–950. https://doi.org/10.1111/ans.18117
Shah NN, Fry TJ (2019) Mechanisms of resistance to CAR T cell therapy. Nat Rev Clin Oncol 16:372–385. https://doi.org/10.1038/s41571-019-0184-6
Shao D, Li J, Xiao X et al (2014) Real-time visualizing and tracing of HSV-TK/GCV suicide gene therapy by near-infrared fluorescent quantum dots. ACS Appl Mater Interfaces 6:11082–11090. https://doi.org/10.1021/am503998x
Sheykhhasan M, Manoochehri H, Dama P (2022) Use of CAR T-cell for acute lymphoblastic leukemia (ALL) treatment: a review study. Cancer Gene Ther 29:1080–1096. https://doi.org/10.1038/s41417-021-00418-1
Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA Cancer J Clin 69:7–34. https://doi.org/10.3322/caac.21551
Singh H, Figliola MJ, Dawson MJ et al (2011) Reprogramming CD19-specific T cells with IL-21 signaling can improve adoptive immunotherapy of B-lineage malignanciesreprogramming CAR+ T cells with IL-21. Cancer Res 71:3516–3527. https://doi.org/10.1158/0008-5472.CAN-10-3843
Slamon DJ, Godolphin W, Jones LA et al (1989) Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244:707–712. https://doi.org/10.1126/science.2470152
Srivastava S, Salter AI, Liggitt D et al (2019) Logic-gated ROR1 chimeric antigen receptor expression rescues T cell-mediated toxicity to normal tissues and enables selective tumor targeting. Cancer Cell 35:489–503. https://doi.org/10.1016/j.ccell.2019.02.003
Stancovski I, Schindler D, Waks T et al (1993) Targeting of T lymphocytes to Neu/HER2-expressing cells using chimeric single chain Fv receptors. J Immunol 151:6577–6582. https://doi.org/10.4049/jimmunol.151.11.6577
Sterner RM, Sakemura R, Cox MJ et al (2019) GM-CSF inhibition reduces cytokine release syndrome and neuroinflammation but enhances CAR-T cell function in xenografts. Blood 133:697–709. https://doi.org/10.1182/blood-2018-10-881722
Subklewe M, von Bergwelt-Baildon M, Humpe A (2019) Chimeric antigen receptor T cells: a race to revolutionize cancer therapy. Transfus Med Hemother 46:15–24. https://doi.org/10.1159/000496870
Sung H, Ferlay J, Siegel RL et al (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209–249. https://doi.org/10.3322/caac.21660
Szöőr Á, Tóth G, Zsebik B et al (2020) Trastuzumab derived HER2-specific CARs for the treatment of trastuzumab-resistant breast cancer: CAR T cells penetrate and eradicate tumors that are not accessible to antibodies. Cancer Lett 484:1–8. https://doi.org/10.1016/j.canlet.2020.04.008
Teng R, Zhao J, Zhao Y et al (2019) Chimeric antigen receptor-modified T cells repressed solid tumors and their relapse in an established patient-derived colon carcinoma xenograft model. J Immunother 42:33. https://doi.org/10.1097/CJI.0000000000000251
Thistlethwaite FC, Gilham DE, Guest RD et al (2017) The clinical efficacy of first-generation carcinoembryonic antigen (CEACAM5)-specific CAR T cells is limited by poor persistence and transient pre-conditioning-dependent respiratory toxicity. Cancer Immunol Immunother 66:1425–1436. https://doi.org/10.1007/s00262-017-2034-7
Tokarew N, Ogonek J, Endres S et al (2019) Teaching an old dog new tricks: next-generation CAR T cells. Br J Cancer 120:26–37. https://doi.org/10.1038/s41416-018-0325-1
Tóth G, Szöllősi J, Abken H et al (2020) A small number of HER2 redirected CAR T cells significantly improves immune response of adoptively transferred mouse lymphocytes against human breast cancer xenografts. Int J Mol Sci 21:1039. https://doi.org/10.3390/ijms21031039
Van Cutsem E, Cervantes A, Adam R et al (2016) ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol 27:1386–1422. https://doi.org/10.1093/annonc/mdw235
Vasaikar SV, Straub P, Wang J et al (2018) LinkedOmics: analyzing multi-omics data within and across 32 cancer types. Nucleic Acids Res 46(D1):D956–D963. https://doi.org/10.1093/nar/gkx1090
Verhoeven Y, Tilborghs S, Jacobs H et al (2020) The potential and controversy of targeting STAT family members in cancer. Semin Cancer Biol 60:41–56. https://doi.org/10.1016/j.semcancer.2019.10.002
Voelker R (2020) CAR-T therapy is approved for mantle cell lymphoma. JAMA 324:832–832. https://doi.org/10.1016/j.semcancer.2019.10.002
Voldborg BR, Damstrup L, Spang-Thomsen M et al (1997) Epidermal growth factor receptor (EGFR) and EGFR mutations, function and possible role in clinical trials. Ann Oncol 8:1197–1206. https://doi.org/10.1023/A:1008209720526
Vora P, Venugopal C, Salim SK et al (2020) The rational development of CD133-targeting immunotherapies for glioblastoma. Cell Stem Cell 26:832–844. https://doi.org/10.1016/j.stem.2020.04.008
Wagener C, Hain F, Födisch HJ et al (1983) Localisation of carcinoembryonic antigen in embryonic and fetal human tissues. Histochemistry 78:1–9. https://doi.org/10.1007/BF00491105
Wagner J, Wickman E, DeRenzo C et al (2020) CAR T cell therapy for solid tumors: bright future or dark reality? Mol Ther 28:2320–2339. https://doi.org/10.1016/j.ymthe.2020.09.015
Wang Z, Wu Z, Liu Y et al (2017) New development in CAR-T cell therapy. J Hematol Oncol 10:53. https://doi.org/10.1186/s13045-017-0423-1
Wang Y, Chen M, Wu Z et al (2018) CD133-directed CAR T cells for advanced metastasis malignancies: a phase I trial. Oncoimmunology 7:e1440169. https://doi.org/10.1080/2162402X.2018.1440169
Warneke V, Behrens H, Haag J et al (2013) Members of the EpCAM signalling pathway are expressed in gastric cancer tissue and are correlated with patient prognosis. Br J Cancer 109:2217–2227. https://doi.org/10.1038/bjc.2013.536
Webb GJ, Hirschfield GM, Lane PJ (2016) OX40, OX40L and autoimmunity: a comprehensive review. Clin Rev Allergy Immunol 50:312–332. https://doi.org/10.1007/s12016-015-8498-3
Weissenstein U, Schumann A, Reif M et al (2012) Detection of circulating tumor cells in blood of metastatic breast cancer patients using a combination of cytokeratin and EpCAM antibodies. BMC Cancer 12:206. https://doi.org/10.1186/1471-2407-12-206
Wickstroem K, Hagemann UB, Cruciani V et al (2019) Synergistic effect of a mesothelin-targeted 227Th conjugate in combination with DNA damage response inhibitors in ovarian cancer xenograft models. J Nucl Med 60:1293–1300. https://doi.org/10.2967/jnumed.118.223701
Wikenheiser DJ, Stumhofer JS (2016) ICOS co-stimulation: friend or foe? Front Immunol 7:304. https://doi.org/10.3389/fimmu.2016.00304
Wu Y, Liu Y, Huang Z et al (2021) Control of the activity of CAR-T cells within tumours via focused ultrasound. Nat Biomed Eng 5:1336–1347. https://doi.org/10.1038/s41551-021-00779-w
Xia L, Zheng Z, Liu J et al (2020) EGFR-targeted CAR-T cells are potent and specific in suppressing triple-negative breast cancer both in vitro and in vivo. Clin Transl Immunol 9:e1135. https://doi.org/10.1002/cti2.1135
Xia L, Zheng Z, Liu J et al (2021) Targeting triple-negative breast cancer with combination therapy of EGFR CAR T cells and CDK7 inhibition targeting TNBC with EGFR CAR T cells and CDK7 inhibition. Cancer Immunol Res 9:707–722. https://doi.org/10.1158/2326-6066.CIR-20-0405
Xie XF, Zhang QY, Huang JY et al (2023) Pyrotinib combined with trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2-positive metastatic breast cancer: a single-arm exploratory phase II trial. Breast Cancer Res Treat 197:93–101. https://doi.org/10.1007/s10549-022-06770-6
Yang P, Cao X, Cai H et al (2021a) The exosomes derived from CAR-T cell efficiently target mesothelin and reduce triple-negative breast cancer growth. Cell Immunol 360:104262. https://doi.org/10.1016/j.cellimm.2020.104262
Yang Y, McCloskey JE, Yang H et al (2021b) Bispecific CAR T cells against EpCAM and inducible ICAM-1 overcome antigen heterogeneity and generate superior antitumor responses bispecific CAR T cells targeting EpCAM and ICAM-1. Cancer Immunol Res 9:1158–1174. https://doi.org/10.1158/2326-6066.CIR-21-0062
Yang YH, Liu JW, Lu C et al (2022) CAR-T cell therapy for breast cancer: from basic research to clinical application. Int J Biol Sci 18:2609. https://doi.org/10.7150/ijbs.70120
Ye B, Stary CM, Li X et al (2018) Engineering chimeric antigen receptor-T cells for cancer treatment. Mol Cancer 17:32. https://doi.org/10.1186/s12943-018-0814-0
Yeku OO, Brentjens RJ (2016) Armored CAR T-cells: utilizing cytokines and pro-inflammatory ligands to enhance CAR T-cell anti-tumour efficacy. Biochem Soc Trans 44:412–418. https://doi.org/10.1042/BST20150291
Yeku OO, Purdon TJ, Koneru M et al (2017) Armored CAR T cells enhance antitumor efficacy and overcome the tumor microenvironment. Sci Rep 7:10541. https://doi.org/10.1038/s41598-017-10940-8
Yin H, Xue W, Anderson DG (2019) CRISPR–Cas: a tool for cancer research and therapeutics. Nat Rev Clin Oncol 16:281–295. https://doi.org/10.1038/s41571-019-0166-8
Yoon DH, Osborn MJ, Tolar J et al (2018) Incorporation of immune checkpoint blockade into chimeric antigen receptor T cells (CAR-Ts): combination or built-in CAR-T. Int J Mol Sci 19:340. https://doi.org/10.3390/ijms19020340
Yu IS, Cheung WY (2018) Metastatic colorectal cancer in the era of personalized medicine: a more tailored approach to systemic therapy. Can J Gastroenterol Hepatol 2018:9450754. https://doi.org/10.1155/2018/9450754
Zhang Y, Deng Z, Liao M et al (2012) Tumor associated glycoprotein-72 is a novel marker for poor survival in hepatocellular carcinoma. Pathol Oncol Res 18:911–916. https://doi.org/10.1007/s12253-012-9521-0
Zhang G, Wang L, Cui H et al (2014) Anti-melanoma activity of T cells redirected with a TCR-like chimeric antigen receptor. Sci Rep 4:3571. https://doi.org/10.1038/srep03571
Zhang C, Liu J, Zhong J et al (2017a) Engineering CAR-T cells. Biomark Res 5:22. https://doi.org/10.1186/s40364-017-0102-y
Zhang C, Wang Z, Yang Z et al (2017b) Phase I escalating-dose trial of CAR-T therapy targeting CEA+ metastatic colorectal cancers. Mol Ther 25:1248–1258. https://doi.org/10.1016/j.ymthe.2017.03.010
Zhang E, Yang P, Gu J et al (2018) Recombination of a dual-CAR-modified T lymphocyte to accurately eliminate pancreatic malignancy. J Hematol Oncol 11:102. https://doi.org/10.1186/s13045-018-0646-9
Zhang BL, Li D, Gong YL et al (2019) Preclinical evaluation of chimeric antigen receptor–modified T cells specific to epithelial cell adhesion molecule for treating colorectal cancer. Hum Gene Ther 30:402–412. https://doi.org/10.1089/hum.2018.229
Zhou R, Yazdanifar M, Roy LD et al (2019) CAR T cells targeting the tumor MUC1 glycoprotein reduce triple-negative breast cancer growth. Front Immunol 10:1149. https://doi.org/10.3389/fimmu.2019.01149
Zhou M, Chen M, Shi B et al (2022) Radiation enhances the efficacy of EGFR-targeted CAR-T cells against triple-negative breast cancer by activating NF-κB/Icam1 signaling. Mol Ther 30:3379–3393. https://doi.org/10.1016/j.ymthe.2022.07.021
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YC, SKY, NMB, MH, XZ, XF, JZ, NBM, KC conceptualized the study; YC, SKY, and NMB Performed the literature analysis and wrote different parts of the original manuscript draft. NMB, KC, JIZ revised, edited, and extended the final draft. All authors have reviewed and approved the manuscript before submission.
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Cao, Y., Efetov, S.K., He, M. et al. Updated Clinical Perspectives and Challenges of Chimeric Antigen Receptor-T Cell Therapy in Colorectal Cancer and Invasive Breast Cancer. Arch. Immunol. Ther. Exp. 71, 19 (2023). https://doi.org/10.1007/s00005-023-00684-x
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DOI: https://doi.org/10.1007/s00005-023-00684-x