Advertisement

Cellular Immunotherapy for Sarcomas

  • Seth M. PollackEmail author
  • Georgios Antoniou
Chapter

Abstract

Adoptive cellular therapy (ACT) is a type of cancer treatment using immune cells, generally lymphocytes, that have undergone ex vivo manipulation, expansion and, in many cases, engineering. ACT is now at a crossroads with the potential to impact every cancer including sarcoma. The alteration of T-cell specificity by genetically modifying them to express well-characterized, high-affinity TCRs allows ACT to target cancers with normal extracellular surface markers presented in the context of the Major Histocompatibility Complex (MHC) proteins. When highly specific markers on the cell surface are available, cancer cells may be best recognized by chimeric antigen receptors (CAR). In this chapter, we will explore efforts to apply ACT both using TCRs and CARs to treat patients with sarcoma.

Keywords

T cell Immunotherapy TCR CAR TIL 

References

  1. 1.
    Burningham Z, Hashibe M, Spector L, Schiffman JD. The epidemiology of Sarcoma. Clin Sarcoma Res. 2012;2:14.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Robert C, Thomas L, Bondarenko I, O’Day S, Weber J, Garbe C, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517–26.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Wolchok JD, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob J-J, Cowey CL, et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2017;377(14):1345–56.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus docetaxel in advanced nonsquamous non–small-cell lung cancer. N Engl J Med. 2015;373(17):1627–39.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Pollack SM, O’Connor TP, Hashash J, Tabbara IA. Nonmyeloablative and reduced-intensity conditioning for allogeneic hematopoietic stem cell transplantation: a clinical review. Am J Clin Oncol. 2009;32(6):618–28.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Matsuda G, Imadome K, Kawano F, Mochizuki M, Ochiai N, Morio T, et al. Cellular immunotherapy with ex vivo expanded cord blood T-cells in a humanized mouse model of EBV-associated lymphoproliferative disease. Immunotherapy. 2015;7(4):335–41.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Kolb H-J. Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood. 2008;112(12):4371–83.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Rooney CM, Smith CA, Ng CY, Loftin S, Li C, Krance RA, et al. Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferation. Lancet. 1995;345(8941):9–13.CrossRefGoogle Scholar
  10. 10.
    Roskrow MA, Suzuki N, Gan YJ, Sixbey JW, Ng CY, Kimbrough S, et al. Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes for the treatment of patients with EBV-positive relapsed Hodgkin’s disease. Blood. 1998;91(8):2925–34.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Lotze MT, Grimm EA, Mazumder A, Strausser JL, Rosenberg SA. Lysis of fresh and cultured autologous tumor by human lymphocytes cultured in T-cell growth factor. Cancer Res. 1981;41(11 Pt 1):4420–5.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Mulé JJ, Shu S, Schwarz SL, Rosenberg SA. Adoptive immunotherapy of established pulmonary metastases with LAK cells and recombinant interleukin-2. Science. 1984;225(4669):1487–9.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Lafreniere R, Rosenberg SA. Successful immunotherapy of murine experimental hepatic metastases with lymphokine-activated killer cells and recombinant interleukin 2. Cancer Res. 1985;45(8):3735–41.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Rosenberg SA. Immunotherapy of cancer by systemic administration of lymphoid cells plus interleukin-2. J Biol Response Mod. 1984;3(5):501–11.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Ettinghausen SE, et al. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med. 1985;313(23):1485–92.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Bogunovic D, O’Neill DW, Belitskaya-Levy I, Vacic V, Yu Y-L, Adams S, et al. Immune profile and mitotic index of metastatic melanoma lesions enhance clinical staging in predicting patient survival. Proc Natl Acad Sci U S A. 2009;106(48):20429–34.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Kilic A, Landreneau RJ, Luketich JD, Pennathur A, Schuchert MJ. Density of tumor-infiltrating lymphocytes correlates with disease recurrence and survival in patients with large non-small-cell lung cancer tumors. J Surg Res. 2011;167(2):207–10.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pagès C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313(5795):1960–4.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Topalian SL, Muul LM, Solomon D, Rosenberg SA. Expansion of human tumor infiltrating lymphocytes for use in immunotherapy trials. J Immunol Methods. 1987;102(1):127–41.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Yuen MF, Norris S. Expression of inhibitory receptors in natural killer (CD3(-)CD56(+)) cells and CD3(+)CD56(+) cells in the peripheral blood lymphocytes and tumor infiltrating lymphocytes in patients with primary hepatocellular carcinoma. Clin Immunol. 2001;101(3):264–9.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Schleypen JS, Baur N, Kammerer R, Nelson PJ, Rohrmann K, Gröne EF, et al. Cytotoxic markers and frequency predict functional capacity of natural killer cells infiltrating renal cell carcinoma. Clin Cancer Res. 2006;12(3 Pt 1):718–25.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Malone CC, Schiltz PM, Mackintosh AD, Beutel LD, Heinemann FS, Dillman RO. Characterization of human tumor-infiltrating lymphocytes expanded in hollow-fiber bioreactors for immunotherapy of cancer. Cancer Biother Radiopharm. 2001;16(5):381–90.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Yron I, Wood TA, Spiess PJ, Rosenberg SA. In vitro growth of murine T-cells. V. The isolation and growth of lymphoid cells infiltrating syngeneic solid tumors. J Immunol. 1980;125(1):238–45.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Muul LM, Spiess PJ, Director EP, Rosenberg SA. Identification of specific cytolytic immune responses against autologous tumor in humans bearing malignant melanoma. J Immunol. 1987;138(3):989–95.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Eberlein TJ, Rosenstein M, Rosenberg SA. Regression of a disseminated syngeneic solid tumor by systemic transfer of lymphoid cells expanded in interleukin 2. J Exp Med. 1982;156(2):385–97.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Rosenberg SA, Spiess P, Lafreniere R. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science. 1986;233(4770):1318–21.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Rosenberg SA, Packard BS, Aebersold PM, Solomon D, Topalian SL, Toy ST, et al. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N Engl J Med. 1988;319(25):1676–80.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Dudley ME, Wunderlich JR, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, et al. A phase I study of nonmyeloablative chemotherapy and adoptive transfer of autologous tumor antigen-specific T lymphocytes in patients with metastatic melanoma. J Immunother. 2002;25(3):243–51.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Dudley ME, Yang JC, Sherry R, Hughes MS, Royal R, Kammula U, et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol. 2008;26(32):5233–9.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Pollack SM, He Q, Yearley JH, Emerson R, Vignali M, Zhang Y, et al. T-cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death-ligand 1 expression in patients with soft tissue sarcomas. Cancer. 2017;123(17):3291–304.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Berghuis D, Santos SJ, Baelde HJ, Taminiau AH, Egeler RM, Schilham MW, et al. Pro-inflammatory chemokine-chemokine receptor interactions within the Ewing sarcoma microenvironment determine CD8(+) T-lymphocyte infiltration and affect tumour progression. J Pathol. 2011;223(3):347–57.CrossRefGoogle Scholar
  32. 32.
    Brinkrolf P, Landmeier S, Altvater B, Chen C, Pscherer S, Rosemann A, et al. A high proportion of bone marrow T-cells with regulatory phenotype (CD4+CD25hiFoxP3+) in Ewing sarcoma patients is associated with metastatic disease. Int J Cancer. 2009;125(4):879–86.CrossRefGoogle Scholar
  33. 33.
    Feng Y, Shen J, Gao Y, Liao Y, Cote G, Choy E. Expression of programmed cell death ligand 1 (PD-L1) and prevalence of tumor-infiltrating lymphocytes (TILs) in chordoma. Oncotarget. 2015;6(13):11139–49.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    D’Angelo SP, Shoushtari AN, Agaram NP, Kuk D, Qin L-X, Carvajal RD, et al. Prevalence of tumor-infiltrating lymphocytes and PD-L1 expression in the soft tissue sarcoma microenvironment. Hum Pathol. 2015;46(3):357–65.CrossRefGoogle Scholar
  35. 35.
    Rusakiewicz S, Semeraro M, Sarabi M, Desbois M, Locher C, Mendez R, et al. Immune infiltrates are prognostic factors in localized gastrointestinal stromal tumors. Cancer Res. 2013;73(12):3499–510.CrossRefGoogle Scholar
  36. 36.
    Fujii H, Arakawa A, Utsumi D, Sumiyoshi S, Yamamoto Y, Kitoh A, et al. CD8+ tumor-infiltrating lymphocytes at primary sites as a possible prognostic factor of cutaneous angiosarcoma. Int J Cancer. 2014;134(10):2393–402.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Sorbye SW, Kilvaer T, Valkov A, Donnem T, Smeland E, Al-Shibli K, et al. Prognostic impact of lymphocytes in soft tissue sarcomas. PLoS ONE. 2011;6(1):e14611.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Sorbye SW, Kilvaer TK, Valkov A, Donnem T, Smeland E, Al-Shibli K, et al. Prognostic impact of peritumoral lymphocyte infiltration in soft tissue sarcomas. BMC Clin Pathol. 2012;12(1):5.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Théoleyre S, Mori K, Cherrier B, Passuti N, Gouin F, Rédini F, et al. Phenotypic and functional analysis of lymphocytes infiltrating osteolytic tumors: use as a possible therapeutic approach of osteosarcoma. BMC Cancer. 2005;5:123.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Van den Eynde B, Lethé B, Van Pel A, De Plaen E, Boon T. The gene coding for a major tumor rejection antigen of tumor P815 is identical to the normal gene of syngeneic DBA/2 mice. J Exp Med. 1991;173(6):1373–84.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Brändle D, Bilsborough J, Rülicke T, Uyttenhove C, Boon T, Van den Eynde BJ. The shared tumor-specific antigen encoded by mouse gene P1A is a target not only for cytolytic T lymphocytes but also for tumor rejection. Eur J Immunol. 1998;28(12):4010–9.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science. 1991;254(5038):1643–7.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Simpson AJG, Caballero OL, Jungbluth A, Chen Y-T, Old LJ. Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer. 2005;5(8):615–25.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Hunder NN, Wallen H, Cao J, Hendricks DW, Reilly JZ, Rodmyre R, et al. Treatment of metastatic melanoma with autologous CD4+ T-cells against NY-ESO-1. N Engl J Med. 2008;358(25):2698–703.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Topalian SL, Gonzales MI, Parkhurst M, Li YF, Southwood S, Sette A, et al. Melanoma-specific CD4+ T-cells recognize nonmutated HLA-DR-restricted tyrosinase epitopes. J Exp Med. 1996;183(5):1965–71.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Ahmed N, Brawley VS, Hegde M, Robertson C, Ghazi A, Gerken C, et al. Human epidermal growth factor receptor 2 (HER2) -specific chimeric antigen receptor-modified T-cells for the immunotherapy of HER2-positive sarcoma. J Clin Oncol. 2015;33(15):1688–96.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Vonderheide RH, Hahn WC, Schultze JL, Nadler LM. The telomerase catalytic subunit is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes. Immunity. 1999;10(6):673–9.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Reker S, Meier A, Holten-Andersen L, Svane IM, Becker JC, Thor SP, et al. Identification of novel survivin-derived ctl epitopes with different HLA-A-restriction profiles. Cancer Biol Ther. 2004;3(2):173–9.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Van den Eynde BJ, van der Bruggen P. T-cell defined tumor antigens. Curr Opin Immunol. 1997;9(5):684–93.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Chapuis AG, Afanasiev OK, Iyer JG, Paulson KG, Parvathaneni U, Hwang JH, et al. Regression of metastatic Merkel cell carcinoma following transfer of polyomavirus-specific T-cells and therapies capable of re-inducing HLA class-I. Cancer Immunol Res. 2014;2(1):27–36.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Mata M, Gottschalk S. Adoptive cell therapy for sarcoma. Immunotherapy. 2015;7(1):21–35.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Chen YT, Scanlan MJ, Sahin U, Türeci O, Gure AO, Tsang S, et al. A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci U S A. 1997;94(5):1914–8.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Szender JB, Papanicolau-Sengos A, Eng KH, Miliotto AJ, Lugade AA, Gnjatic S, et al. NY-ESO-1 expression predicts an aggressive phenotype of ovarian cancer. Gynecol Oncol. 2017;145(3):420–5.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Iura K, Kohashi K, Hotokebuchi Y, Ishii T, Maekawa A, Yamada Y, et al. Cancer-testis antigens PRAME and NY-ESO-1 correlate with tumour grade and poor prognosis in myxoid liposarcoma. J Pathol Clin Res. 2015;1(3):144–59.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Davis ID, Chen W, Jackson H, Parente P, Shackleton M, Hopkins W, et al. Recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad integrated antibody and CD4(+) and CD8(+) T-cell responses in humans. Proc Natl Acad Sci U S A. 2004;101(29):10697–702.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Nicholaou T, Ebert LM, Davis ID, McArthur GA, Jackson H, Dimopoulos N, et al. Regulatory T-cell-mediated attenuation of T-cell responses to the NY-ESO-1 ISCOMATRIX vaccine in patients with advanced malignant melanoma. Clin Cancer Res. 2009;15(6):2166–73.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Scanlan MJ, Simpson AJG, Old LJ. The cancer/testis genes: review, standardization, and commentary. Cancer Immun. 2004;4:1.Google Scholar
  58. 58.
    Jungbluth AA, Antonescu CR, Busam KJ, Iversen K, Kolb D, Coplan K, et al. Monophasic and biphasic synovial sarcomas abundantly express cancer/testis antigen NY-ESO-1 but not MAGE-A1 or CT7. Int J Cancer. 2001;94(2):252–6.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Chapuis AG, Thompson JA, Margolin KA, Rodmyre R, Lai IP, Dowdy K, et al. Transferred melanoma-specific CD8+ T-cells persist, mediate tumor regression, and acquire central memory phenotype. Proc Natl Acad Sci U S A. 2012;109(12):4592–7.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Pollack SM, Jungbluth AA, Hoch BL, Farrar EA, Bleakley M, Schneider DJ, et al. NY-ESO-1 is a ubiquitous immunotherapeutic target antigen for patients with myxoid/round cell liposarcoma. Cancer. 2012;118(18):4564–70.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Yee C, Savage PA, Lee PP, Davis MM, Greenberg PD. Isolation of high avidity melanoma-reactive CTL from heterogeneous populations using peptide-MHC tetramers. J Immunol. 1999;162(4):2227–34.PubMedPubMedCentralGoogle Scholar
  62. 62.
    Bodinier M, Peyrat MA, Tournay C, Davodeau F, Romagne F, Bonneville M, et al. Efficient detection and immunomagnetic sorting of specific T-cells using multimers of MHC class I and peptide with reduced CD8 binding. Nat Med. 2000;6(6):707–10.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Meidenbauer N, Marienhagen J, Laumer M, Vogl S, Heymann J, Andreesen R, et al. Survival and tumor localization of adoptively transferred Melan-A-specific T-cells in melanoma patients. J Immunol. 2003;170(4):2161–9.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Mackensen A, Meidenbauer N, Vogl S, Laumer M, Berger J, Andreesen R. Phase I study of adoptive T-cell therapy using antigen-specific CD8+ T-cells for the treatment of patients with metastatic melanoma. J Clin Oncol. 2006;24(31):5060–9.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Khammari A, Labarrière N, Vignard V, Nguyen J-M, Pandolfino M-C, Knol AC, et al. Treatment of metastatic melanoma with autologous Melan-A/MART-1-specific cytotoxic T lymphocyte clones. J Invest Dermatol. 2009;129(12):2835–42.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Yee C, Thompson JA, Byrd D, Riddell SR, Roche P, Celis E, et al. Adoptive T-cell therapy using antigen-specific CD8+ T-cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T-cells. Proc Natl Acad Sci U S A. 2002;99(25):16168–73.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Provasi E, Genovese P, Magnani Z, Pello OM, Kuball J, Lombardo A, et al. From TCR gene transfer to TCR gene editing of central memory T lymphocytes for immunotherapy of leukemia. Blood. 2009;114(22):374.Google Scholar
  68. 68.
    Morgan RA, Dudley ME, Yu YYL, Zheng Z, Robbins PF, Theoret MR, et al. High efficiency TCR gene transfer into primary human lymphocytes affords avid recognition of melanoma tumor antigen glycoprotein 100 and does not alter the recognition of autologous melanoma antigens. J Immunol. 2003;171(6):3287–95.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Robbins PF, Morgan RA, Feldman SA, Yang JC, Sherry RM, Dudley ME, et al. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol. 2011;29(7):917–24.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Robbins PF, Kassim SH, Tran TLN, Crystal JS, Morgan RA, Feldman SA, et al. A pilot trial using lymphocytes genetically engineered with an NY-ESO-1-reactive T-cell receptor: long-term follow-up and correlates with response. Clin Cancer Res. 2015;21(5):1019–27.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Turtle CJ, Hanafi L-A, Berger C, Gooley TA, Cherian S, Hudecek M, et al. CD19 CAR-T-cells of defined CD4+:CD8+ composition in adult B cell ALL patients. J Clin Invest. 2016;126(6):2123–38.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA. Case report of a serious adverse event following the administration of T-cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther. 2010;18(4):843–51.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Huang G, Yu L, Cooper LJ, Hollomon M, Huls H, Kleinerman ES. Genetically modified T-cells targeting interleukin-11 receptor α-chain kill human osteosarcoma cells and induce the regression of established osteosarcoma lung metastases. Cancer Res. 2012;72(1):271–81.PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Lehner M, Götz G, Proff J, Schaft N, Dörrie J, Full F, et al. Redirecting T-cells to Ewing’s sarcoma family of tumors by a chimeric NKG2D receptor expressed by lentiviral transduction or mRNA transfection. PLoS ONE. 2012;7(2):e31210.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Gattenlöhner S, Marx A, Markfort B, Pscherer S, Landmeier S, Juergens H, et al. Rhabdomyosarcoma lysis by T-cells expressing a human autoantibody-based chimeric receptor targeting the fetal acetylcholine receptor. Cancer Res. 2006;66(1):24–8.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Fry TJ, Shah NN, Orentas RJ, Stetler-Stevenson M, Yuan CM, Ramakrishna S, et al. CD22-targeted CAR T-cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat Med. 2017;24(1):20–8.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Tanaka M, Tashiro H, Omer B, Lapteva N, Ando J, Ngo M, et al. Vaccination targeting native receptors to enhance the function and proliferation of chimeric antigen receptor (CAR)-modified T-cells. Clin Cancer Res. 2017;23(14):3499–509.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    A phase I trial of T-cells expressing an anti-GD2 chimeric antigen receptor in children and young adults with GD2+ solid tumors - full text view - ClinicalTrials.gov [internet]. [cited 2018 Jan 24]. Available from: https://clinicaltrials.gov/ct2/show/NCT02107963.
  79. 79.
    Pegram HJ, Lee JC, Hayman EG, Imperato GH, Tedder TF, Sadelain M, et al. Tumor-targeted T-cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning. Blood. 2012;119(18):4133–41.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Sadelain M, Rivière I, Brentjens R. Targeting tumours with genetically enhanced T lymphocytes. Nat Rev Cancer. 2003;3(1):35–45.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Cheng LE, Ohlén C, Nelson BH, Greenberg PD. Enhanced signaling through the IL-2 receptor in CD8+ T-cells regulated by antigen recognition results in preferential proliferation and expansion of responding CD8+ T-cells rather than promotion of cell death. Proc Natl Acad Sci U S A. 2002;99(5):3001–6.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Rosenberg SA, Sherry RM, Morton KE, Scharfman WJ, Yang JC, Topalian SL, et al. Tumor progression can occur despite the induction of very high levels of self/tumor antigen-specific CD8+ T-cells in patients with melanoma. J Immunol. 2005;175(9):6169–76.PubMedCrossRefPubMedCentralGoogle Scholar
  84. 84.
    Ratnavelu K, Subramani B, Pullai CR, Krishnan K, Sugadan SD, Rao MS, et al. Autologous immune enhancement therapy against an advanced epithelioid sarcoma: A case report. Oncol Lett. 2013;5(5):1457–60.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Clinical Research DivisionFred Hutchinson Cancer Research CenterSeattleUSA
  2. 2.Division of OncologyUniversity of WashingtonSeattleUSA
  3. 3.Sarcoma UnitThe Royal Marsden Hospital NHS Foundation TrustLondonUK

Personalised recommendations