Skip to main content
SpringerLink
Log in

T Lymphocytes with Modified Specificity in the Therapy of Malignant Diseases

  • Current Trends in the Application of Monoclonal Antibodies Special Issue
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract

Immunotherapy is one of the most rapidly progressing and promising fields in antitumor therapy. It is based on the idea of using immune cells of patient or healthy donors for elimination of malignant cells. T lymphocytes play a key role in cell-mediated immunity including the response to tumors. Recently developed approaches of altering antigen specificity of T cells consist of their genetic modification (introduction of additional T cell receptor or chimeric antigen receptor), as well as the use of bispecific molecules that crosslink target and effector cells. These approaches are used to retarget T lymphocytes with arbitrary specificity against tumor antigens in the context of antitumor immunotherapy. The high potential of T cell immunotherapy was demonstrated in a number of clinical trials. In the future, it is possible to develop approaches to the therapy of a wide spectrum of tumors. The selection of the optimal antigen is the main challenge in successful T cell immunotherapy, as it largely determines the effectiveness of the treatment, as well as the risk of side effects. In this review we discuss potential methods of modification of T cell specificity and targets for immunotherapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Schreiber R.D., Old L.J., Smyth M.J. 2011. Cancer immunoediting: Integrating immunity’s roles in cancer suppression and promotion. Science. 331 (6024), 1565–1570.

    Article  CAS  PubMed  Google Scholar 

  2. Burnet F.M. 1967. Immunological aspects of malignant disease. Lancet. 1 (7501), 1171–1174.

    Article  CAS  PubMed  Google Scholar 

  3. Burne F.M. 1970. The concept of immunological surveillance. Prog. Exp. Tumor Res. 13, 1–27.

    Article  Google Scholar 

  4. Thomas L. 1982. On immunosurveillance in human cancer. Yale J. Biol. Med. 55 (3–4), 329–333.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Pradeu T., Vivier E. 2016. The discontinuity theory of immunity. Sci. Immunol. 1 (1), aag0479.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Poggi A., Zocchi M.R. 2006. Mechanisms of tumor escape: Role of tumor microenvironment in inducing apoptosis of cytolytic effector cells. Arch. Immunol. Ther. Exp. 54 (5), 323–333.

    Article  CAS  Google Scholar 

  7. Adler A.J. 2007. Mechanisms of T cell tolerance and suppression in cancer mediated by tumor-associated antigens and hormones. Curr. Cancer Drug Targets. 7 (1), 3–14.

    Article  CAS  PubMed  Google Scholar 

  8. Lee S., Margolin K. 2011. Cytokines in cancer immunotherapy. Cancers. 3 (4), 3856–3893.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Rosenberg S.A., Lotze M.T., Muul L.M., et al. 1985. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N. Eng. J. Med. 313 (23), 1485–1492.

    Article  CAS  Google Scholar 

  10. Kirkwood J. 2002. Cancer immunotherapy: The interferon- alpha experience. Semin. Oncol. 29 (3, Suppl. 7), 18–26.

    Article  CAS  PubMed  Google Scholar 

  11. Morgan D.A., Ruscetti F.W., Gallo R. 1976. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science. 193 (4257), 1007–1008.

    Article  CAS  PubMed  Google Scholar 

  12. Kumar S.K., Vij R., Noga S.J., et al. 2017. Treating multiple myeloma patients with oral therapies. Clin. Lymphoma Myeloma Leuk. 17 (5), 243–251.

    Article  PubMed  Google Scholar 

  13. Oldfield V., Keating G.M., Perry C.M. 2005. Imiquimod: In superficial basal cell carcinoma. Am. J. Clin. Dermatol. 6 (3), 195–200; discussion 201–192.

    Article  PubMed  Google Scholar 

  14. Breyer J., Burger M., Otto W. 2016. Immunotherapy in urothelial carcinoma: Fade or future standard? Transl. Androl. Urol. 5 (5), 662–667.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Melero I., Hervas-Stubbs S., Glennie M., et al. 2007. Immunostimulatory monoclonal antibodies for cancer therapy. Nat. Rev. Cancer. 7 (2), 95–106.

    Article  CAS  PubMed  Google Scholar 

  16. Topalian S.L., Taube J.M., Anders R.A., et al. 2016. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat. Rev. Cancer. 16 (5), 275–287.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bogolyubova A.V., Efimov G.A., Drutskaya M.S., et al. 2015. Cancer immunotherapy based on the blockade of immune checkpoints. Med. Immunol. (Russ.). 17 (5), 395–406.

    Article  Google Scholar 

  18. Holmes J.P., Clifton G.T., Patil R., et al. 2011. Use of booster inoculations to sustain the clinical effect of an adjuvant breast cancer vaccine: From US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Cancer. 117 (3), 463–471.

    Article  CAS  PubMed  Google Scholar 

  19. Rosenberg S.A., Yang J.C., Sherry R.M., et al. 2011. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin. Cancer Res. 17 (13), 4550–4557.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Rosenberg S.A., Spiess P., Lafreniere R. 1986. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science. 233 (4770), 1318–1321.

    Article  CAS  PubMed  Google Scholar 

  21. Huh J.W., Lee J.H., Kim H.R. 2012. Prognostic significance of tumor-infiltrating lymphocytes for patients with colorectal cancer. Arch. Surg. 147 (4), 366–372.

    Article  PubMed  Google Scholar 

  22. Reynders K., De Ruysscher D. 2016. Tumor infiltrating lymphocytes in lung cancer: A new prognostic parameter. J. Thorac. Dis. 8 (8), E833–E835.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kawata A., Une Y., Hosokawa M., et al. 1992. Tumorinfiltrating lymphocytes and prognosis of hepatocellular carcinoma. Jpn. J. Clin. Oncol. 22 (4), 256–263.

    CAS  PubMed  Google Scholar 

  24. Theoleyre S., Mori K., Cherrier B., et al. 2005. Phenotypic and functional analysis of lymphocytes infiltrating osteolytic tumors: Use as a possible therapeutic approach of osteosarcoma. BMC Cancer. 5, 123–132.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Chapuis A.G., Desmarais C., Emerson R., et al. 2017. Tracking the fate and origin of clinically relevant adoptively transferred CD8+ T cells in vivo. Sci. Immunol. 2 (8), 1–11. doi 10.1126/sciimmunol.aal2568

    Article  Google Scholar 

  26. Schwartzentruber D.J., Lawson D.H., Richards J.M., et al. 2011. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. New Engl. J. Med. 364 (22), 2119–2127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Bonifaz L.C., Bonnyay D.P., Charalambous A., et al. 2004. In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination. J. Exp. Med. 199 (6), 815–824.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Paczesny S., Banchereau J., Wittkowski K.M., et al. 2004. Expansion of melanoma-specific cytolytic CD8+ T cell precursors in patients with metastatic melanoma vaccinated with CD34+ progenitor-derived dendritic cells. J. Exp. Med. 199 (11), 1503–1511.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Schumacher T.N., Schreiber R.D. 2015. Neoantigens in cancer immunotherapy. Science. 348 (6230), 69–74.

    Article  CAS  PubMed  Google Scholar 

  30. Kvistborg P., Shu C.J., Heemskerk B., et al. 2012. TIL therapy broadens the tumor-reactive CD8+ T cell compartment in melanoma patients. Oncoimmunology. 1 (4), 409–418.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Andersen R.S., Thrue C.A., Junker N., et al. 2012. Dissection of T-cell antigen specificity in human melanoma. Cancer Res. 72 (7), 1642–1650.

    Article  CAS  PubMed  Google Scholar 

  32. Vigneron N. 2015. Human tumor antigens and cancer immunotherapy. BioMed Res. Int. 2015, 948501 1–17.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Sato S., Ono N., Steeber D.A., et al. 1996. CD19 regulates B lymphocyte signaling thresholds critical for the development of B-1 lineage cells and autoimmunity. J. Immunol. 157 (10), 4371–4378.

    CAS  PubMed  Google Scholar 

  34. Naddafi F., Davami F. 2015. Anti-CD19 monoclonal antibodies: A new approach to lymphoma therapy. Int. J. Mol. Cell. Med. 4 (3), 143–151.

    PubMed  PubMed Central  Google Scholar 

  35. Cooper L.J., Al-Kadhimi Z., DiGiusto D., et al. 2004. Development and application of CD19-specific T cells for adoptive immunotherapy of B cell malignancies. Blood Cell. Mol. Dis. 33 (1), 83–89.

    Article  CAS  Google Scholar 

  36. Vallera D.A., Chen H., Sicheneder A.R., et al. 2009. Genetic alteration of a bispecific ligand-directed toxin targeting human CD19 and CD22 receptors resulting in improved efficacy against systemic B cell malignancy. Leukemia Res. 33 (9), 1233–1242.

    Article  CAS  Google Scholar 

  37. Kuppers R. 2005. Mechanisms of B-cell lymphoma pathogenesis. Nat. Rev. Cancer. 5 (4), 251–262.

    Article  PubMed  CAS  Google Scholar 

  38. Cheever M.A., Allison J.P., Ferris A.S., et al. 2009. The prioritization of cancer antigens: A national cancer institute pilot project for the acceleration of translational research. Clin. Cancer Res. 15 (17), 5323–5337.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Tashiro H., Brenner M.K. 2017. Immunotherapy against cancer-related viruses. Cell Res. 27 (1), 59–73.

    Article  CAS  PubMed  Google Scholar 

  40. Kanakry J.A., Ambinder R.F. 2013. EBV-related lymphomas: New approaches to treatment. Curr. Treat. Options Oncol. 14 (2), 224–236.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Ramos C.A., Narala N., Vyas G.M., et al. 2013. Human papillomavirus type 16 E6/E7-specific cytotoxic T lymphocytes for adoptive immunotherapy of HPV-associated malignancies. J. Immunother. 36 (1), 66–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Chun E., Lee J., Cheong H.S., et al. 2003. Tumor eradication by hepatitis B virus X antigen-specific CD8+ T cells in xenografted nude mice. J. Immunol. 170 (3), 1183–1190.

    Article  CAS  PubMed  Google Scholar 

  43. Zhang Y., Liu Y., Moxley K.M., et al. 2010. Transduction of human T cells with a novel T-cell receptor confers anti-HCV reactivity. PLoS Pathog. 6 (7), e1001018 1–13.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Stevanovic S., Pasetto A., Helman S.R., et al. 2017. Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer. Science. 356 (6334), 200–205.

    Article  CAS  PubMed  Google Scholar 

  45. Efimov G.A., Vdovin A.S., Grigoryev A.A., et al. 2015. Immunobiology of acute graft-versus-host disease. Med. Immunol. (Russ.). 17 (6), 499–516.

    Article  Google Scholar 

  46. Shlomchik W.D. 2007. Graft-versus-host disease. Nat. Rev. Immunol. 7 (5), 340–352.

    Article  CAS  PubMed  Google Scholar 

  47. Bleakley M., Riddell S.R. 2011. Exploiting T cells specific for human minor histocompatibility antigens for therapy of leukemia. Immunol. Cell Biol. 89 (3), 396–407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Griffioen M., van Bergen C.A., Falkenburg J.H. 2016. Autosomal minor histocompatibility antigens: How genetic variants create diversity in immune targets. Front. Immunol. 7 (100), 1–9.

    Google Scholar 

  49. Bykova N.A., Malko D.B., Vdovin A.S., et al. 2016. In silico analysis of single nucleotide polymorphism immunogenic potential in fully HLA-matched transplantation. Ross. Immunol. Zh. 10 (1), 38–48.

    Google Scholar 

  50. Heemskerk M.H., Hoogeboom M., de Paus R.A., et al. 2003. Redirection of antileukemic reactivity of peripheral T lymphocytes using gene transfer of minor histocompatibility antigen HA-2-specific T-cell receptor complexes expressing a conserved alpha joining region. Blood. 102 (10), 3530–3540.

    Article  CAS  PubMed  Google Scholar 

  51. Obenaus M., Leitao C., Leisegang M., et al. 2015. Identification of human T-cell receptors with optimal affinity to cancer antigens using antigen-negative humanized mice. Nat. Biotechnol. 33 (4), 402–407.

    Article  CAS  PubMed  Google Scholar 

  52. Jackson H.J., Rafiq S., Brentjens R.J. 2016. Driving CAR T-cells forward. Nat. Rev. Clin. Oncol. 13 (6), 370–383.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Frankel S.R., Baeuerle P.A. 2013. Targeting T cells to tumor cells using bispecific antibodies. Curr. Opin. Chem. Biol. 17 (3), 385–392.

    Article  CAS  PubMed  Google Scholar 

  54. Mahnke Y.D., Brodie T.M., Sallusto F., et al. 2013. The who’s who of T-cell differentiation: Human memory T-cell subsets. Eur. J. Immunol. 43 (11), 2797–2809.

    Article  CAS  PubMed  Google Scholar 

  55. Klebanoff C.A., Gattinoni L., Palmer D.C., et al. 2011. Determinants of successful CD8+ T-cell adoptive immunotherapy for large established tumors in mice. Clin. Canc. Res. 17 (16), 5343–5352.

    Article  CAS  Google Scholar 

  56. Gattinoni L., Lugli E., Ji Y., et al. 2011. A human memory T cell subset with stem cell-like properties. Nat. Med. 17 (10), 1290–1297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Sommermeyer D., Hudecek M., Kosasih P.L., et al. 2016. Chimeric antigen receptor-modified T cells derived from defined CD8+ and CD4+ subsets confer superior antitumor reactivity in vivo. Leukemia. 30 (2), 492–500.

    Article  CAS  PubMed  Google Scholar 

  58. Shedlock D.J., Shen H. 2003. Requirement for CD4 T cell help in generating functional CD8 T cell memory. Science. 300 (5617), 337–339.

    Article  CAS  PubMed  Google Scholar 

  59. Moeller M., Haynes N.M., Kershaw M.H., et al. 2005. Adoptive transfer of gene-engineered CD4+ helper T cells induces potent primary and secondary tumor rejection. Blood. 106 (9), 2995–3003.

    Article  CAS  PubMed  Google Scholar 

  60. Matsuzaki J., Tsuji T., Luescher I.F., et al. 2015. Direct tumor recognition by a human CD4+ T-cell subset potently mediates tumor growth inhibition and orchestrates anti-tumor immune responses. Sci. Repts. 5, 14896 1–14.

    Article  CAS  Google Scholar 

  61. Turtle C.J., Hanafi L.A., Berger C., et al. 2016. CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. J. Clin. Invest. 126 (6), 2123–2138.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Pule M.A., Savoldo B., Myers G.D., et al. 2008. Virus-specific T cells engineered to coexpress tumorspecific receptors: Persistence and antitumor activity in individuals with neuroblastoma. Nat. Med. 14 (11), 1264–1270.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Rossig C., Bar A., Pscherer S., et al. 2006. Target antigen expression on a professional antigen-presenting cell induces superior proliferative antitumor T-cell responses via chimeric T-cell receptors. J. Immunother. 29 (1), 21–31.

    Article  CAS  PubMed  Google Scholar 

  64. Nakazawa Y., Huye L.E., Salsman V.S., et al. 2011. PiggyBac-mediated cancer immunotherapy using EBV-specific cytotoxic T-cells expressing HER2-specific chimeric antigen receptor. Mol. Ther.: J. Am. Soc. Gene Ther. 19 (12), 2133–2143.

    Article  CAS  Google Scholar 

  65. Savoldo B., Rooney C.M., Di Stasi A., et al. 2007. Epstein Barr virus-specific cytotoxic T lymphocytes expressing the anti-CD30zeta artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease. Blood. 110 (7), 2620–2630.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Vdovin A.S., Filkin S.Y., Yefimova P.R., et al. 2016. Recombinant MHC tetramers for isolation of virusspecific CD8+ cells from healthy donors: Potential approach for cell therapy of posttransplant cytomegalovirus infection. Biochemistry (Moscow). 81 (11), 1371–1383.

    Article  CAS  PubMed  Google Scholar 

  67. Lim W.A., June C.H. 2017. The principles of engineering immune cells to treat cancer. Cell. 168 (4), 724–740.

    Article  CAS  PubMed  Google Scholar 

  68. Johnson L.A., Heemskerk B., Powell D.J. Jr., et al. 2006. Gene transfer of tumor-reactive TCR confers both high avidity and tumor reactivity to nonreactive peripheral blood mononuclear cells and tumor-infiltrating lymphocytes. J. Iimmunol. 177 (9), 6548–6559.

    Article  CAS  Google Scholar 

  69. Hughes M.S., Yu Y.Y., Dudley M.E., et al. 2005. Transfer of a TCR gene derived from a patient with a marked antitumor response conveys highly active T-cell effector functions. Hum. Gene Ther. 16 (4), 457–472.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Cole D.J., Weil D.P., Shilyansky J., et al. 1995. Characterization of the functional specificity of a cloned T-cell receptor heterodimer recognizing the MART-1 melanoma antigen. Cancer Res. 55 (4), 748–752.

    CAS  PubMed  Google Scholar 

  71. Morgan R.A., Dudley M.E., Wunderlich J.R., et al. 2006. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science. 314 (5796), 126–129.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Johnson L.A., Morgan R.A., Dudley M.E., et al. 2009. Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood. 114 (3), 535–546.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Dossinger G., Bunse M., Bet J., et al. 2013. MHC multimer-guided and cell culture-independent isolation of functional T cell receptors from single cells facilitates TCR identification for immunotherapy. PLoS ONE. 8 (4), e61384.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Wang G.C., Dash P., McCullers J.A., et al. 2012. T cell receptor alphabeta diversity inversely correlates with pathogen-specific antibody levels in human cytomegalovirus infection. Sci. Translat. Med. 4 (128), 128ra142.

    Article  Google Scholar 

  75. Linnemann C., Heemskerk B., Kvistborg P., et al. 2013. High-throughput identification of antigen-specific TCRs by TCR gene capture. Nat. Med. 19 (11), 1534–1541.

    Article  CAS  PubMed  Google Scholar 

  76. Linnemann C., Mezzadra R., Schumacher T.N. 2014. TCR repertoires of intratumoral T-cell subsets. Immunol. Rev. 257 (1), 72–82.

    Article  CAS  PubMed  Google Scholar 

  77. Gao L., Bellantuono I., Elsasse A., et al. 2000. Selective elimination of leukemic CD34+ progenitor cells by cytotoxic T lymphocytes specific for WT1. Blood. 95 (7), 2198–2203.

    CAS  PubMed  Google Scholar 

  78. Stanislawski T., Voss R.H., Lotz C., et al. 2001. Circumventing tolerance to a human MDM2-derived tumor antigen by TCR gene transfer. Nat. Immunol. 2 (10), 962–970.

    Article  CAS  PubMed  Google Scholar 

  79. Zhao Y., Bennett A.D., Zheng Z., et al. 2007. Highaffinity TCRs generated by phage display provide CD4+ T cells with the ability to recognize and kill tumor cell lines. J. Immunol. 179 (9), 5845–5854.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Khamaganova E.G., Kuzminova E.P., Yushkova A.A., et al. 2016. Distribution of HLA-haplotypes in the bone marrow donor register of National Research Center for Hematology of the Russian Ministry of Health. Hematol. Transfusiol. 61 (S1), 78.

    Google Scholar 

  81. van Loenen M.M., de Boer R., Amir A.L. et al. 2010. Mixed T cell receptor dimers harbor potentially harmful neoreactivity. Proc. Natl. Acad. Sci. U. S. A. 107 (24), 10972–10977.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Bendle G.M., Linnemann C., Hooijkaas A.I., et al. 2010. Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy. Nat. Med. 16 (5), 565–570.

    Article  CAS  PubMed  Google Scholar 

  83. Starck L., Popp K., Pircher H., et al. 2014. Immunotherapy with TCR-redirected T cells: Comparison of TCR-transduced and TCR-engineered hematopoietic stem cell-derived T cells. J. Immunol. 192 (1), 206–213.

    Article  PubMed  CAS  Google Scholar 

  84. Hart D.P., Xue S.A., Thomas S., et al. 2008. Retroviral transfer of a dominant TCR prevents surface expression of a large proportion of the endogenous TCR repertoire in human T cells. Gene Ther. 15 (8), 625–631.

    Article  CAS  PubMed  Google Scholar 

  85. Bunse M., Bendle G.M., Linnemann C., et al. 2014. RNAi-mediated TCR knockdown prevents autoimmunity in mice caused by mixed TCR dimers following TCR gene transfer. Mol. Ther. 22 (11), 1983–1991.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Ridgway J.B., Presta L.G., Carter P. 1996. ‘Knobsinto- holes’ engineering of antibody CH3 domains for heavy chain heterodimerization. Protein Eng. 9 (7), 617–621.

    Article  CAS  PubMed  Google Scholar 

  87. Parkhurst M.R., Yang J.C., Langan R.C., et al. 2011. T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Mol. Ther. 19 (3), 620–626.

    Article  CAS  PubMed  Google Scholar 

  88. Morgan R.A., Chinnasamy N., Abate-Daga D., et al. 2013. Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy. J. Immunother. 36 (2), 133–151.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Robbins P.F., Kassim S.H., Tran T.L., et al. 2015. A pilot trial using lymphocytes genetically engineered with an NY-ESO-1-reactive T-cell receptor: Longterm follow-up and correlates with response. Clin. Cancer Res. 21 (5), 1019–1027.

    Article  CAS  PubMed  Google Scholar 

  90. Sadelain M., Brentjens R., Riviere I. 2013. The basic principles of chimeric antigen receptor design. Cancer Discov. 3 (4), 388–398.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Kershaw M.H., Westwood J.A., Parker L.L., et al. 2006. A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin. Cancer Res. 12 (20, Pt. 1), 6106–6115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Lamers C.H., Sleijfer S., Vulto A.G., et al. 2006. Treatment of metastatic renal cell carcinoma with autologous T-lymphocytes genetically retargeted against carbonic anhydrase IX: First clinical experience. J. Clin. Oncol. 24 (13), e20–e22.

    Article  PubMed  Google Scholar 

  93. Park J.R., Digiusto D.L., Slovak M., et al. 2007. Adoptive transfer of chimeric antigen receptor redirected cytolytic T lymphocyte clones in patients with neuroblastoma. Mol. Ther. 15 (4), 825–833.

    Article  CAS  PubMed  Google Scholar 

  94. Ahmed N., Brawley V.S., Hegde M., et al. 2015. Human epidermal growth factor receptor 2 (HER2)- specific chimeric antigen receptor-modified T cells for the immunotherapy of HER2-positive sarcoma. J. Clin.Oncol. 33 (15), 1688–1696.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Brown C.E., Badie B., Barish M.E., et al. 2015. Bioactivity and safety of IL13Ralpha2-redirected chimeric antigen receptor CD8+ T cells in patients with recurrent glioblastoma. Clin. Cancer Res. 21 (18), 4062–4072.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Kochenderfer J.N., Wilson W.H., Janik J.E., et al. 2010. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood. 116 (20), 4099–4102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Kochenderfer J.N., Dudley M.E., Feldman S.A., et al. 2012. B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood. 119 (12), 2709–2720.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Porter D.L., Levine B.L., Kalos M., et al. 2011. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N. Eng. J. Med. 365 (8), 725–733.

    Article  CAS  Google Scholar 

  99. Morgan R.A., Yang J.C., 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 (4), 843–851.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Davila M.L., Riviere I., Wang X., et al. 2014. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci. Transl. Med. 6 (224), 224–225.

    Article  CAS  Google Scholar 

  101. Grupp S.A., Kalos M., Barrett D., et al. 2013. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N. Eng. J. Med. 368 (16), 1509–1518.

    Article  CAS  Google Scholar 

  102. Maude S.L., Frey N., Shaw P.A., et al. 2014. Chimeric antigen receptor T cells for sustained remissions in leukemia. N. Eng. J. Med. 371 (16), 1507–1517.

    Article  CAS  Google Scholar 

  103. Lee D.W., Kochenderfer J.N., Stetler-Stevenson M., et al. 2015. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: A phase 1 dose-escalation trial. Lancet. 385 (9967), 517–528.

    Article  CAS  PubMed  Google Scholar 

  104. Yang F., Wen W., Qin W. 2016. Bispecific antibodies as a development platform for new concepts and treatment strategies. Int. J. Mol. Sci. 18 (1), 48 1–21.

    Article  PubMed Central  Google Scholar 

  105. Spiess C., Zhai Q., Carter P.J. 2015. Alternative molecular formats and therapeutic applications for bispecific antibodies. Mol. Immunol. 67 (2, Pt. A), 95–106.

    Article  CAS  PubMed  Google Scholar 

  106. Chames P., Baty D. 2009. Bispecific antibodies for cancer therapy: The light at the end of the tunnel? MAbs. 1 (6), 539–547.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Manzke O., Titzer S., Tesch H., et al. 1997. CD3 × CD19 bispecific antibodies and CD28 costimulation for locoregional treatment of low-malignancy non- Hodgkin’s lymphoma. Cancer Immunol. Immunother. 45 (3–4), 198–202.

    Article  CAS  PubMed  Google Scholar 

  108. Shen J., Zhu Z. 2008. Catumaxomab, a rat/murine hybrid trifunctional bispecific monoclonal antibody for the treatment of cancer.Curr. Opin. Mol. Ther. 10 (3), 273–284.

    CAS  Google Scholar 

  109. Spizzo G., Went P., Dirnhofer S., et al. 2004. High Ep-CAM expression is associated with poor prognosis in node-positive breast cancer. Breast Cancer Res. Treat. 86 (3), 207–213.

    Article  CAS  PubMed  Google Scholar 

  110. Spizzo G., Went P., Dirnhofer S., et al. 2006. Overexpression of epithelial cell adhesion molecule (Ep- CAM) is an independent prognostic marker for reduced survival of patients with epithelial ovarian cancer. Gynecol. Oncol. 103 (2), 483–488.

    Article  CAS  PubMed  Google Scholar 

  111. Went P., Vasei M., Bubendorf L., et al. 2006. Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers. Br. J. Cancer. 94 (1), 128–135.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Lindhofer H., Mocikat R., Steipe, B., et al. 1995. Preferential species-restricted heavy/light chain pairing in rat/mouse quadromas. Implications for a single-step purification of bispecific antibodies. J. Immunol. 155 (1), 219–225.

    CAS  PubMed  Google Scholar 

  113. Kiewe P., Hasmuller. S., Kahler S., et al. 2006. Phase I trial of the trifunctional anti-HER2 × anti-CD3 antibody ertumaxomab in metastatic breast cancer. Clin. Cancer Res. 12 (10), 3085–3091.

    Article  CAS  PubMed  Google Scholar 

  114. Buhmann R., Simoes B., Stanglmaier M., et al. 2009. Immunotherapy of recurrent B-cell malignancies after allo-SCT with Bi20 (FBTA05), a trifunctional anti- CD3 × anti-CD20 antibody and donor lymphocyte infusion. Bone Marrow Transplant. 43 (5), 383–397.

    Article  CAS  PubMed  Google Scholar 

  115. Ruf P., Jager M., Ellwart J., et al. 2004. Two new trifunctional antibodies for the therapy of human malignant melanoma. Int. J. Cancer. 108 (5), 725–732.

    Article  CAS  PubMed  Google Scholar 

  116. Dreier T., Baeuerle P.A., Fichtner I., et al. 2003. T cell costimulus-independent and very efficacious inhibition of tumor growth in mice bearing subcutaneous or leukemic human B cell lymphoma xenografts by a CD19-/CD3- bispecific single-chain antibody construct. J. Immunol. 170 (8), 4397–4402.

    Article  CAS  PubMed  Google Scholar 

  117. Schlereth B., Quadt C., Dreier T., et al. 2006. T-cell activation and B-cell depletion in chimpanzees treated with a bispecific anti-CD19/anti-CD3 single-chain antibody construct. Cancer Immunol. Immunother. 55 (5), 503–514.

    Article  CAS  PubMed  Google Scholar 

  118. Bargou R., Leo E., Zugmaier G., et al. 2008. Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science. 321 (5891), 974–977.

    Article  CAS  PubMed  Google Scholar 

  119. Mack M., Riethmuller G., Kufer P. 1995. A small bispecific antibody construct expressed as a functional single-chain molecule with high tumor cell cytotoxicity. Proc. Natl. Acad. Sci. U. S. A. 92 (15), 7021–7025.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Loffler A., Kufer P., Lutterbuse R., et al. 2000. A recombinant bispecific single-chain antibody, CD19 × CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes. Blood. 95 (6), 2098–2103.

    CAS  PubMed  Google Scholar 

  121. Brischwein K., Parr L., Pflanz S., et al. 2007. Strictly target cell-dependent activation of T cells by bispecific single-chain antibody constructs of the BiTE class. J. Immunother. 30 (8), 798–807.

    Article  CAS  PubMed  Google Scholar 

  122. Amann M., D’Argouges S., Lorenczewski G., et al. 2009. Antitumor activity of an EpCAM/CD3-bispe cific BiTE antibody during long-term treatment of mice in the absence of T-cell anergy and sustained cytokine release. J. Immunother. 32 (5), 452–464.

    Article  CAS  PubMed  Google Scholar 

  123. Hoffmann P., Hofmeister R., Brischwein K., et al. 2005. Serial killing of tumor cells by cytotoxic T cells redirected with a CD19-/CD3- bispecific single-chain antibody construct. Int. J. Cancer. 115 (1), 98–104.

    Article  CAS  PubMed  Google Scholar 

  124. Ferrari F., Bellone S., Black J., et al. 2015. Solitomab, an EpCAM/CD3 bispecific antibody construct (BiTE (R)), is highly active against primary uterine and ovarian carcinosarcoma cell lines in vitro. J. Exp. Clin. Cancer Res. 34, 123. doi 10.1186/s13046-015-0241-7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  125. Lutterbuese R., Wissing S., Amann M., et al. 2008. Conversion of Cetuximab and Trastuzumab into T cell-engaging BiTE antibodies creates novel drug candidates with superior anti-tumor activity. Cancer Res. 68 (9, Suppl.), 2402–2402.

    Google Scholar 

  126. Liddy N., Bossi G., Adams K.J., et al. 2012. Monoclonal TCR-redirected tumor cell killing. Nat. Med. 18 (6), 980–987.

    Article  CAS  PubMed  Google Scholar 

  127. Bossi G., Buisson S., Oates J., et al. 2014. ImmTACredirected tumour cell killing induces and potentiates antigen cross-presentation by dendritic cells. Cancer Immunol. Immunother. 63 (5), 437–448.

    Article  CAS  PubMed  Google Scholar 

  128. McCormack E., Adams K.J., Hassan N.J., et al. 2013. Bi-specific TCR-anti CD3 redirected T-cell targeting of NY-ESO-1- and LAGE-1-positive tumors. Cancer Immunol. Immunother. 62 (4), 773–785.

    Article  CAS  PubMed  Google Scholar 

  129. Oates J., Jakobsen B.K. 2013. ImmTACs: Novel bispecific agents for targeted cancer therapy. Oncoimmunology. 2 (2), e22891 1–3.

    Article  PubMed  PubMed Central  Google Scholar 

  130. Pecorari F., Tissot A.C., Pluckthun A. 1999. Folding, heterodimeric association and specific peptide recognition of a murine alphabeta T-cell receptor expressed in Escherichia coli. J. Mol. Biol. 285 (4), 1831–1843.

    Article  CAS  PubMed  Google Scholar 

  131. Schodin B.A., Schlueter C.J., Kranz D.M. 1996. Binding properties and solubility of single-chain T cell receptors expressed in E. coli. Mol. Immunol. 33 (9), 819–829.

    Article  CAS  PubMed  Google Scholar 

  132. Boulter J.M., Glick M., Todorov P.T., et al. 2003. Stable, soluble T-cell receptor molecules for crystallization and therapeutics. Protein Eng. 16 (9), 707–711.

    Article  CAS  PubMed  Google Scholar 

  133. Cole D.K., Yuan F., Rizkallah P.J., et al. 2009. Germ line-governed recognition of a cancer epitope by an immunodominant human T-cell receptor. J. Biol. Chem. 284 (40), 27281–27289.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Li Y., Moysey R., Molloy P.E., et al. 2005. Directed evolution of human T-cell receptors with picomolar affinities by phage display. Nat. Biotechnol. 23 (3), 349–354.

    Article  CAS  PubMed  Google Scholar 

  135. Dunn S.M., Rizkallah P.J., Baston E., et al. 2006. Directed evolution of human T cell receptor CDR2 residues by phage display dramatically enhances affinity for cognate peptide-MHC without increasing apparent cross-reactivity. Protein Sci. 15 (4), 710–721.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Sergeeva A., Alatrash G., He H., et al. 2011. An anti- PR1/HLA-A2 T-cell receptor-like antibody mediates complement-dependent cytotoxicity against acute myeloid leukemia progenitor cells. Blood. 117 (16), 4262–4272.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Wittman V.P., Woodburn D., Nguyen T., et al. 2006. Antibody targeting to a class I MHC-peptide epitope promotes tumor cell death. J. Immunol. 177 (6), 4187–4195.

    Article  CAS  PubMed  Google Scholar 

  138. Chames P., Willemsen R.A., Rojas G., et al. 2002. TCR-like human antibodies expressed on human CTLs mediate antibody affinity-dependent cytolytic activity. J. Immunol. 169 (2), 1110–1118.

    Article  CAS  PubMed  Google Scholar 

  139. Stewart-Jones G., Wadle A., Hombach A., et al. 2009. Rational development of high-affinity T-cell receptorlike antibodies. Proc. Natl. Acad. Sci. U. S. A. 106 (14), 5784–5788.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Denkberg G., Lev A., Eisenbach L., et al. 2003. Selective targeting of melanoma and APCs using a recombinant antibody with TCR-like specificity directed toward a melanoma differentiation antigen. J. Immunol. 171 (5), 2197–2207.

    Article  CAS  PubMed  Google Scholar 

  141. Krogsgaard M., Wucherpfennig K.W., Cannella B., et al. 2000. Visualization of myelin basic protein (MBP. T cell epitopes in multiple sclerosis lesions using a monoclonal antibody specific for the human histocompatibility leukocyte antigen (HLA)-DR2-MBP 85-99 complex. J. Exp. Med. 191 (8), 1395–1412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Miller K.R., Koide A., Leung B., et al. 2012. T cell receptor-like recognition of tumor in vivo by synthetic antibody fragment. PLoS ONE. 7 (8), e43746.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Cohen M., Reiter Y., (2013). T-cell receptor-like antibodies: Targeting the intracellular proteome therapeutic potential and clinical applications. Antibodies. 2 (3), 517–534.

  144. Spanier J.A., Frederick D.R., Taylor J.J., et al. 2016. Efficient generation of monoclonal antibodies against peptide in the context of MHCII using magnetic enrichment. Nat. Commun. 7, 11804, 1–11.

    Google Scholar 

  145. Dao T., Pankov D., Scott A., et al. 2015. Therapeutic bispecific T-cell engager antibody targeting the intracellular oncoprotein WT1. Nat. Biotechnol. 33 (10), 1079–1086.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Dao T., Korontsvit T., Zakhaleva V., et al. 2017. An immunogenic WT1-derived peptide that induces T cell response in the context of HLA-A*02:01 and HLA-A*24:02 molecules. Oncoimmunology. 6 (2), e1252895.

    Article  PubMed  CAS  Google Scholar 

  147. Friedman M., Stahl S. 2009. Engineered affinity proteins for tumour-targeting applications. Biotechnol. Appl. Biochem. 53 (1), 1–29.

    Article  CAS  PubMed  Google Scholar 

  148. Gorchakov A.A., Kulemzin S.V., Volkova O.Yu., et al. 2016. Chimeric antigenic receptors for adaptive T-cell therapy. Ross. Bioterapevt. Zh. 15 (1), 25–26.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. National Research Center for Hematology, Ministry of Healthcare of the Russian Federation, Moscow, 125167, Russia

    A. S. Vdovin, N. A. Bykova & G. A. Efimov

Authors
  1. A. S. Vdovin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. A. Bykova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. A. Efimov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. A. Efimov.

Additional information

Original Russian Text © A.S. Vdovin, N.A. Bykova, G.A. Efimov, 2017, published in Molekulyarnaya Biologiya, 2017, Vol. 51, No. 6, pp. 1008–1023.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vdovin, A.S., Bykova, N.A. & Efimov, G.A. T Lymphocytes with Modified Specificity in the Therapy of Malignant Diseases. Mol Biol 51, 874–886 (2017). https://doi.org/10.1134/S0026893317060164

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893317060164

Keywords

Search

Navigation