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Involving stemness factors to improve CAR T-cell-based cancer immunotherapy

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Abstract

Treatment with chimeric antigen receptor (CAR) T cells indicated remarkable clinical responses with liquid cancers such as hematological malignancies; however, their therapeutic efficacy faced with many challenges in solid tumors due to severe toxicities, antigen evasion, restricted and limited tumor tissue trafficking and infiltration, and, more importantly, immunosuppressive tumor microenvironment (TME) factors that impair the CAR T-cell function adds support survival of cancer stem cells (CSCs), responsible for tumor recurrence and resistance to current cancer therapies. Therefore, in-depth identification of TME and development of more potent CAR platform targeting CSCs may overcome the raised challenges, as presented in this review. We also discuss recent stemness-based innovations in CAR T-cell production and engineering to improve their efficacy in vivo, and finally, we propose solutions and strategies such as oncolytic virus-based therapy and combination therapy to revive the function of CAR T-cell therapy, especially in TME of solid tumors in future.

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Abbreviations

ACT:

Adoptive cell therapy

CAR:

Chimeric antigen receptor

CRS:

Cytokine-release syndrome

CSCs:

Cancer stem cells

DAMPs:

Damage-associated molecular patterns

ICB:

Immune checkpoint blockade

iCARs:

Inhibitory CARs

ICIs:

Immune checkpoint inhibitors

iPSCs:

Induced pluripotent stem cells

GvHD:

Graft-versus-host disease

PAMPs:

Pathogen-associated molecular patterns

PBMC:

Peripheral blood mononuclear cell

MDSCs:

Myeloid-derived suppressor cells

OV:

Oncolytic virus

TAAs:

Tumor-associated antigens

TAMs:

Tumor-associated macrophages

TILs:

Tumor-infiltrating lymphocytes

TME:

Tumor microenvironment

References

  1. Arumugam V, Bluemn T, Wesley E, Schmidt AM, Kambayashi T, Malarkannan S, et al. TCR signaling intensity controls CD8+ T cell responsiveness to TGF-β. J Leukoc Biol. 2015;98(5):703–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. June CH, O’Connor RS, Kawalekar OU, Ghassemi S, Milone MC. CAR T cell immunotherapy for human cancer. Science. 2018;359(6382):1361–5.

    Article  CAS  PubMed  Google Scholar 

  3. Chmielewski M, Hombach AA, Abken H. Of CAR s and TRUCKs: chimeric antigen receptor (CAR) T cells engineered with an inducible cytokine to modulate the tumor stroma. Immunol Rev. 2014;257(1):83–90.

    Article  CAS  PubMed  Google Scholar 

  4. D’Aloia MM, Zizzari IG, Sacchetti B, Pierelli L, Alimandi M. CAR-T cells: the long and winding road to solid tumors. Cell Death Dis. 2018;9(3):282.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Zhang Y, He L, Sadagopan A, Ma T, Dotti G, Wang Y, et al. Targeting radiation-resistant prostate cancer stem cells by B7–H3 CAR T cells. Mol Cancer Ther. 2021;20(3):577–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Mohammadzadeh H, Babaniamansour S, Majidi M, Zare A, Dehghani Firouzabadi M, Karkon-Shayan S. Merkel cell carcinoma on the right calf in association with chronic lymphocytic leukemia: a case report. Clin Case Rep. 2021;9(7):e04498.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Stingl J, Caldas C. Molecular heterogeneity of breast carcinomas and the cancer stem cell hypothesis. Nat Rev Cancer. 2007;7(10):791–9.

    Article  CAS  PubMed  Google Scholar 

  8. Mahmoodi S, Nezafat N, Negahdaripour M, Ghasemi Y. A new approach for cancer immunotherapy based on the cancer stem cell antigens properties. Curr Mol Med. 2019;19(1):2–11.

    Article  CAS  PubMed  Google Scholar 

  9. Afshari AR, Motamed-Sanaye A, Sabri H, Soltani A, Karkon-Shayan S, Radvar S, et al. Neurokinin-1 receptor (NK-1R) antagonists: potential targets in the treatment of glioblastoma multiforme. Curr Med Chem. 2021;28(24):4877–92.

    Article  CAS  PubMed  Google Scholar 

  10. Zhu X, Prasad S, Gaedicke S, Hettich M, Firat E, Niedermann G. Patient-derived glioblastoma stem cells are killed by CD133-specific CAR T cells but induce the T cell aging marker CD57. Oncotarget. 2015;6(1):171.

    Article  PubMed  Google Scholar 

  11. Munz M, Baeuerle PA, Gires O. The emerging role of EpCAM in cancer and stem cell signaling. Can Res. 2009;69(14):5627–9.

    Article  CAS  Google Scholar 

  12. Yamashita T, Ji J, Budhu A, Forgues M, Yang W, Wang HY, et al. EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology. 2009;136(3):1012–24.

    Article  CAS  PubMed  Google Scholar 

  13. Zhang B-L, Li D, Gong Y-L, Huang Y, Qin D-Y, Jiang L, et al. Preclinical evaluation of chimeric antigen receptor–modified T cells specific to epithelial cell adhesion molecule for treating colorectal cancer. Hum Gene Ther. 2019;30(4):402–12.

    Article  PubMed  Google Scholar 

  14. Tettamanti S, Marin V, Pizzitola I, Magnani CF, Giordano Attianese GM, Cribioli E, et al. Targeting of acute myeloid leukaemia by cytokine-induced killer cells redirected with a novel CD 123-specific chimeric antigen receptor. Br J Haematol. 2013;161(3):389–401.

    Article  CAS  PubMed  Google Scholar 

  15. Dai H, Tong C, Shi D, Chen M, Guo Y, Chen D, et al. Efficacy and biomarker analysis of CD133-directed CAR T cells in advanced hepatocellular carcinoma: a single-arm, open-label, phase II trial. Oncoimmunology. 2020;9(1):1846926.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kutsch N, Gödel P, Holtick U, Lohneis A, Vucinic V, Altefrohne FP, et al. A phase I dose finding trial of MB-CART20.1 in patients with relapsed or refractory B-cell non-hodgkin lymphoma. Blood. 2022;140:12980–1.

    Article  Google Scholar 

  17. Huang H, Wu H-W, Hu Y-X. Current advances in chimeric antigen receptor T-cell therapy for refractory/relapsed multiple myeloma. J Zhejiang Univ Sci B. 2020;21(1):29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Deng Z, Wu Y, Ma W, Zhang S, Zhang Y-Q. Adoptive T-cell therapy of prostate cancer targeting the cancer stem cell antigen EpCAM. BMC Immunol. 2015;16(1):1–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. El Khawanky N, Hughes A, Yu W, Myburgh R, Matschulla T, Taromi S, et al. Demethylating therapy increases anti-CD123 CAR T cell cytotoxicity against acute myeloid leukemia. Nat Commun. 2021;12(1):6436.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Tchou J, Zhao Y, Levine BL, Zhang PJ, Davis MM, Melenhorst JJ, et al. Safety and efficacy of intratumoral injections of chimeric antigen receptor (CAR) T cells in metastatic breast cancer. Cancer Immunol Res. 2017;5(12):1152–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ali S, Toews K, Schwiebert S, Klaus A, Winkler A, Grunewald L, et al. Tumor-derived extracellular vesicles impair CD171-specific CD4+ CAR T cell efficacy. Front Immunol. 2020;11:531.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Gong X, Azhdarinia A, Ghosh SC, Xiong W, An Z, Liu Q, et al. LGR5-targeted antibody-drug conjugate eradicates gastrointestinal tumors and prevents recurrence LGR5-targeted ADC eradicates gastrointestinal tumors. Mol Cancer Ther. 2016;15(7):1580–90.

    Article  CAS  PubMed  Google Scholar 

  23. Li C, Wu JJ, Hynes M, Dosch J, Sarkar B, Welling TH, et al. c-Met is a marker of pancreatic cancer stem cells and therapeutic target. Gastroenterology. 2011;141(6):2218–27.

    Article  CAS  PubMed  Google Scholar 

  24. Thayaparan T, Petrovic RM, Achkova DY, Zabinski T, Davies DM, Klampatsa A, et al. CAR T-cell immunotherapy of MET-expressing malignant mesothelioma. Oncoimmunology. 2017;6(12):e1363137.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Kikushige Y, Miyamoto T, Yuda J, Jabbarzadeh-Tabrizi S, Shima T, Takayanagi S-I, et al. A TIM-3/Gal-9 autocrine stimulatory loop drives self-renewal of human myeloid leukemia stem cells and leukemic progression. Cell Stem Cell. 2015;17(3):341–52.

    Article  CAS  PubMed  Google Scholar 

  26. Li X, Bu W, Meng L, Liu X, Wang S, Jiang L, et al. CXCL12/CXCR4 pathway orchestrates CSC-like properties by CAF recruited tumor associated macrophage in OSCC. Exp Cell Res. 2019;378(2):131–8.

    Article  CAS  PubMed  Google Scholar 

  27. Welte T, Kim IS, Tian L, Gao X, Wang H, Li J, et al. Oncogenic mTOR signalling recruits myeloid-derived suppressor cells to promote tumour initiation. Nat Cell Biol. 2016;18(6):632–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Shidal C, Singh NP, Nagarkatti P, Nagarkatti M. MicroRNA-92 expression in CD133+ melanoma stem cells regulates immunosuppression in the tumor microenvironment via integrin-dependent activation of TGFβ. Can Res. 2019;79(14):3622–35.

    Article  CAS  Google Scholar 

  29. Kuroda H, Mabuchi S, Yokoi E, Komura N, Kozasa K, Matsumoto Y, et al. Prostaglandin E2 produced by myeloid-derived suppressive cells induces cancer stem cells in uterine cervical cancer. Oncotarget. 2018;9(91):36317.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Mahic M, Yaqub S, Johansson CC, Taskén K, Aandahl EM. FOXP3+ CD4+ CD25+ adaptive regulatory T cells express cyclooxygenase-2 and suppress effector T cells by a prostaglandin E2-dependent mechanism. J Immunol. 2006;177(1):246–54.

    Article  CAS  PubMed  Google Scholar 

  31. Boroughs AC, Larson RC, Choi BD, Bouffard AA, Riley LS, Schiferle E, et al. Chimeric antigen receptor costimulation domains modulate human regulatory T cell function. JCI Insight. 2019;4(8):6194.

    Article  Google Scholar 

  32. Zhang H, Yu P, Tomar VS, Chen X, Atherton MJ, Lu Z, et al. Targeting PARP11 to avert immunosuppression and improve CAR T therapy in solid tumors. Nat Cancer. 2022;3:1–13.

    Article  Google Scholar 

  33. Rad SMAH, Halpin JC, Tawinwung S, Suppipat K, Hirankarn N, McLellan AD. MicroRNA-mediated metabolic reprogramming of chimeric antigen receptor T cells. Immunol Cell Biol. 2022;100(6):424–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Shen L, Xiao Y, Zhang C, Li S, Teng X, Cui L, et al. Metabolic reprogramming by ex vivo glutamine inhibition endows CAR-T cells with less-differentiated phenotype and persistent antitumor activity. Cancer Lett. 2022;538:215710.

    Article  CAS  PubMed  Google Scholar 

  35. Montel-Hagen A, Seet CS, Li S, Chick B, Zhu Y, Chang P, et al. Organoid-induced differentiation of conventional T cells from human pluripotent stem cells. Cell Stem Cell. 2019;24(3):376–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Iriguchi S, Yasui Y, Kawai Y, Arima S, Kunitomo M, Sato T, et al. A clinically applicable and scalable method to regenerate T-cells from iPSCs for off-the-shelf T-cell immunotherapy. Nat Commun. 2021;12(1):1–15.

    Article  Google Scholar 

  37. Minagawa A, Yoshikawa T, Yasukawa M, Hotta A, Kunitomo M, Iriguchi S, et al. Enhancing T cell receptor stability in rejuvenated iPSC-derived T cells improves their use in cancer immunotherapy. Cell Stem Cell. 2018;23(6):850–8.

    Article  CAS  PubMed  Google Scholar 

  38. Keshavarz M, Ebrahimzadeh MS, Miri SM, Dianat-Moghadam H, Ghorbanhosseini SS, Mohebbi SR, et al. Oncolytic Newcastle disease virus delivered by mesenchymal stem cells-engineered system enhances the therapeutic effects altering tumor microenvironment. Virol J. 2020;17(1):1–13.

    Google Scholar 

  39. Guo ZS, Liu Z, Bartlett DL. Oncolytic immunotherapy: dying the right way is a key to eliciting potent antitumor immunity. Front Oncol. 2014;4:74.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Shahgolzari M, Dianat-Moghadam H, Fiering S. Multifunctional plant virus nanoparticles in the next generation of cancer immunotherapies. Semin Cancer Biol. 2022;86:1076.

    Article  CAS  PubMed  Google Scholar 

  41. Liu Y, Cai J, Liu W, Lin Y, Guo L, Liu X, et al. Intravenous injection of the oncolytic virus M1 awakens antitumor T cells and overcomes resistance to checkpoint blockade. Cell Death Dis. 2020;11(12):1062.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Moon EK, Wang L-CS, Bekdache K, Lynn RC, Lo A, Thorne SH, et al. Intra-tumoral delivery of CXCL11 via a vaccinia virus, but not by modified T cells, enhances the efficacy of adoptive T cell therapy and vaccines. Oncoimmunology. 2018;7(3):e1395997.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Nishio N, Dotti G. Oncolytic virus expressing RANTES and IL-15 enhances function of CAR-modified T cells in solid tumors. Oncoimmunology. 2015;4(2):e988098.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Chen L, Zhou C, Chen Q, Shang J, Liu Z, Guo Y, et al. Oncolytic Zika virus promotes intratumoral T cell infiltration and improves immunotherapy efficacy in glioblastoma. Mol Ther-Oncol. 2022;24:522–34.

    Article  CAS  Google Scholar 

  45. Nguyen H-M, Guz-Montgomery K, Saha D. Oncolytic virus encoding a master pro-inflammatory cytokine interleukin 12 in cancer immunotherapy. Cells. 2020;9(2):400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Chen T, Ding X, Liao Q, Gao N, Chen Y, Zhao C, et al. IL-21 arming potentiates the anti-tumor activity of an oncolytic vaccinia virus in monotherapy and combination therapy. J Immunother Cancer. 2021;9(1):e001647.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Gujar S, Pol JG, Kim Y, Lee PW, Kroemer G. Antitumor benefits of antiviral immunity: an underappreciated aspect of oncolytic virotherapies. Trends Immunol. 2018;39(3):209–21.

    Article  CAS  PubMed  Google Scholar 

  48. Rezaei R, Esmaeili Gouvarchin Ghaleh H, Farzanehpour M, Dorostkar R, Ranjbar R, Bolandian M, et al. Combination therapy with CAR T cells and oncolytic viruses: a new era in cancer immunotherapy. Cancer Gene Ther. 2021;29:1–14.

    Google Scholar 

  49. Keshavarz M, Miri SM, Behboudi E, Arjeini Y, Dianat-Moghadam H, Ghaemi A. Oncolytic virus delivery modulated immune responses toward cancer therapy: challenges and perspectives. Int Immunopharmacol. 2022;108:108882.

    Article  CAS  PubMed  Google Scholar 

  50. Azani A, Omran SP, Ghasrsaz H, Idani A, Kadkhodaei Eliaderani M, Peirovi N, et al. MicroRNAs as biomarkers for early diagnosis, targeting and prognosis of prostate cancer. Pathol Res Pract. 2023;248:154618.

    Article  CAS  PubMed  Google Scholar 

  51. Weiss T, Weller M, Guckenberger M, Sentman CL, Roth P. NKG2D-based CAR T cells and radiotherapy exert synergistic efficacy in glioblastoma radiotherapy augments NKG2D CAR T cells against glioblastoma. Can Res. 2018;78(4):1031–43.

    Article  CAS  Google Scholar 

  52. Lynn RC, Poussin M, Kalota A, Feng Y, Low PS, Dimitrov DS, et al. Targeting of folate receptor β on acute myeloid leukemia blasts with chimeric antigen receptor-expressing T cells. Blood. 2015;125(22):3466–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Dianat-Moghadam H, Mahari A, Salahlou R, Khalili M, Azizi M, Sadeghzadeh H. Immune evader cancer stem cells direct the perspective approaches to cancer immunotherapy. Stem Cell Res Ther. 2022;13(1):1–12.

    Article  Google Scholar 

  54. Wang J, Deng Q, Jiang YY, Zhang R, Zhu HB, Meng JX, et al. CAR-T 19 combined with reduced-dose PD-1 blockade therapy for treatment of refractory follicular lymphoma: a case report. Oncol Lett. 2019;18(5):4415–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Yamaguchi Y, Gibson J, Ou K, Lopez LS, Ng RH, Leggett N, et al. PD-L1 blockade restores CAR T cell activity through IFN-γ-regulation of CD163+ M2 macrophages. J Immunother Cancer. 2022;10(6):e004400.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Nix MA, Mandal K, Geng H, Paranjape N, Lin Y-HT, Rivera JM, et al. Surface proteomics reveals CD72 as a target for in vitro-evolved nanobody-based CAR-T cells in KMT2A/MLL1-rearranged B-ALLCD72 nanobody-based CAR-T in MLLr B-ALL. Cancer Discov. 2021;11(8):2032–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Theruvath J, Sotillo E, Mount CW, Graef CM, Delaidelli A, Heitzeneder S, et al. Locoregionally administered B7-H3-targeted CAR T cells for treatment of atypical teratoid/rhabdoid tumors. Nat Med. 2020;26(5):712–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Zhang E, Yang P, Gu J, Wu H, Chi X, Liu C, et al. Recombination of a dual-CAR-modified T lymphocyte to accurately eliminate pancreatic malignancy. J Hematol Oncol. 2018;11(1):1–14.

    Article  Google Scholar 

  59. Fedorov VD, Themeli M, Sadelain M. PD-1 and CTLA-4-based inhibitory chimeric antigen receptors (iCARs) divert off-target immunotherapy responses. Sci Transl Med. 2013;5(215):215.

    Article  Google Scholar 

  60. Liu L, Liu Y, Xia Y, Wang G, Zhang X, Zhang H, et al. Synergistic killing effects of PD-L1-CAR T cells and colorectal cancer stem cell-dendritic cell vaccine-sensitized T cells in ALDH1-positive colorectal cancer stem cells. J Cancer. 2021;12(22):6629.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Budde LE, Berger C, Lin Y, Wang J, Lin X, Frayo SE, et al. Combining a CD20 chimeric antigen receptor and an inducible caspase 9 suicide switch to improve the efficacy and safety of T cell adoptive immunotherapy for lymphoma. PLoS ONE. 2013;8(12):e82742.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Drent E, Poels R, Ruiter R, van de Donk NW, Zweegman S, Yuan H, et al. Combined CD28 and 4–1BB costimulation potentiates affinity-tuned chimeric antigen receptor-engineered T cells dual costimulation empowers very low-affinity CAR-T cells. Clin Cancer Res. 2019;25(13):4014–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Maroun J, Muñoz-Alía M, Ammayappan A, Schulze A, Peng K-W, Russell S. Designing and building oncolytic viruses. Future Virol. 2017;12(4):193–213.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Miest TS, Yaiw K-C, Frenzke M, Lampe J, Hudacek AW, Springfeld C, et al. Envelope-chimeric entry-targeted measles virus escapes neutralization and achieves oncolysis. Mol Ther. 2011;19(10):1813–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Oncology and Metabolism, University of Tabuk, Tabuk, Saudi Arabia

    Sara Abdalrazzaq M. Noraldeen

  2. School of Humanities, Natural & Social Sciences, New Uzbekistan University, 54 Mustaqillik Ave., 100007, Tashkent, Uzbekistan

    Irodakhon Rasulova

  3. Department of Pharmaceutical Analysis, Chaitanya Deemed to be University, Hyderabad, Telangana, India

    Repudi Lalitha

  4. Medical Technical College, Al-Farahidi University, Baghdad, Iraq

    Farah Hussin

  5. Department of Pharmaceutics and Pharmaceutical Technology, Taif University, 21944, Taif, Saudi Arabia

    Hashem O. Alsaab

  6. College of Technical Engineering, The Islamic University, Najaf, Iraq

    Ahmed Hussien Alawadi

  7. College of Technical Engineering, The Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq

    Ahmed Hussien Alawadi

  8. College of Technical Engineering, The Islamic University of Babylon, Babylon, Iraq

    Ahmed Hussien Alawadi

  9. College of Technical Engineering, Imam Ja’afar Al‐Sadiq University, Al‐Muthanna, 66002, Iraq

    Ali Alsaalamy

  10. College of Nursing, National University of Science and Technology, Dhi Qar, Iraq

    Nidhal Hassan Sayyid

  11. Cardiology Department, College of Medicine, Al-Ayen University, Thi-Qar, Iraq

    Adnan Taan Alkhafaji

  12. Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul, 41001, Iraq

    Yasser Fakri Mustafa

  13. Student Research Committee, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran

    Sepideh Karkon Shayan

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  1. Sara Abdalrazzaq M. Noraldeen
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Contributions

S.A.N, I.R, F.H, H.O.A, A.H.A, A.A, N.H.S, A.T.A, and Y.F.M contributed to investigation and writing original/revised draft. R.L and S.K.Sh contributed to conceptualization, investigation, writing original draft, writing-review & editing, visualization, supervision, and project administration. All co-authors approved the final version of the manuscript.

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Correspondence to Repudi Lalitha or Sepideh Karkon Shayan.

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Noraldeen, S.A.M., Rasulova, I., Lalitha, R. et al. Involving stemness factors to improve CAR T-cell-based cancer immunotherapy. Med Oncol 40, 313 (2023). https://doi.org/10.1007/s12032-023-02191-7

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