open access

Vol 15, No 4 (2019)
Review paper
Published online: 2019-08-21
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A novel immunotherapy — the history of CAR T-cell therapy

Ewa Wrona, Piotr Potemski
DOI: 10.5603/OCP.2019.0016
·
Oncol Clin Pract 2019;15(4):202-207.

open access

Vol 15, No 4 (2019)
REVIEW ARTICLES
Published online: 2019-08-21

Abstract

Robust research over the past 30 years has led recently to the first approval of genetically enhanced T lymphocytes expressing chimeric antigen receptors (CAR T-cells) as a tool to fight cancer. The backbone of the aforementioned therapy is to equip patients’ T lymphocytes in a genetically modified receptor that can recognise the antigen present on the surface of a cancer cell with the accuracy of a specific antibody, and to ignite a cytotoxic reaction against it with the function of the T-lymphocyte receptor. Ground-breaking results achieved in patients with haematological malignancies led to multiple clinical trials of CAR T-cell-based therapy in solid tumours. Regardless of the initial hurdles, recent reports suggest that continuous evolution and further improvements of CAR T-cell therapy for solid tumours is as successful as that observed in haematology. Despite the fact that enormous efforts are still to be made, implementation of CAR T-cells into the clinical oncologist’s daily routine practice was never as plausible as it is today.

Abstract

Robust research over the past 30 years has led recently to the first approval of genetically enhanced T lymphocytes expressing chimeric antigen receptors (CAR T-cells) as a tool to fight cancer. The backbone of the aforementioned therapy is to equip patients’ T lymphocytes in a genetically modified receptor that can recognise the antigen present on the surface of a cancer cell with the accuracy of a specific antibody, and to ignite a cytotoxic reaction against it with the function of the T-lymphocyte receptor. Ground-breaking results achieved in patients with haematological malignancies led to multiple clinical trials of CAR T-cell-based therapy in solid tumours. Regardless of the initial hurdles, recent reports suggest that continuous evolution and further improvements of CAR T-cell therapy for solid tumours is as successful as that observed in haematology. Despite the fact that enormous efforts are still to be made, implementation of CAR T-cells into the clinical oncologist’s daily routine practice was never as plausible as it is today.
Get Citation

Keywords

personalised medicine; genetic modifications; CAR T-cell therapy; solid tumours; haematological malignancies

About this article
Title

A novel immunotherapy — the history of CAR T-cell therapy

Journal

Oncology in Clinical Practice

Issue

Vol 15, No 4 (2019)

Article type

Review paper

Pages

202-207

Published online

2019-08-21

DOI

10.5603/OCP.2019.0016

Bibliographic record

Oncol Clin Pract 2019;15(4):202-207.

Keywords

personalised medicine
genetic modifications
CAR T-cell therapy
solid tumours
haematological malignancies

Authors

Ewa Wrona
Piotr Potemski

References (29)
  1. June C, O’Connor R, Kawalekar O, et al. CAR T cell immunotherapy for human cancer. Science. 2018; 359(6382): 1361–1365.
  2. Yong C, Dardalhon V, Devaud C, et al. CAR T-cell therapy of solid tumors. Immunology and Cell Biology. 2017; 95(4): 356–363.
  3. Gross G, Waks T, Eshhar Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci U S A. 1989; 86(24): 10024–10028.
  4. News W, America N. Emily Whitehead : girl whose cancer was ’cured’ by HIV. 2012. https://www.telegraph.co.uk/news/worldnews/northamerica/usa/9738355/Emily-Whitehead-girl-whose-cancer-was-cured-by-HIV.html.
  5. Androulla M, Lefkothea P. CAR T-cell Therapy: A New Era in Cancer Immunotherapy. Current Pharmaceutical Biotechnology. 2018; 19(1): 5–18.
  6. Levine BL, Miskin J, Wonnacott K, et al. Global Manufacturing of CAR T Cell Therapy. Mol Ther Methods Clin Dev. 2017; 4: 92–101.
  7. Qasim W, Zhan H, Samarasinghe S, et al. Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells. Sci Transl Med. 2017; 9(374).
  8. FDA. Full prescribing information: axicabtagene ciloleucel. 2017. https://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM581226.pdf.
  9. FDA. Full prescribing information: tisagenlecleucel. 2017. https://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM573941.pdf.
  10. Maude S, Frey N, Shaw P, et al. Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia. New England Journal of Medicine. 2014; 371(16): 1507–1517.
  11. Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med. 2018; 378(5): 439–448.
  12. Neelapu S, Locke F, Bartlett N, et al. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. New England Journal of Medicine. 2017; 377(26): 2531–2544.
  13. Abramson JS, Palomba L, Gordon LI, et al. Transcend NHL 001: Immunotherapy with the CD19-Directed CAR T-Cell Product JCAR017 Results in High Complete Response Rates in Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma. Blood 2016;128(22):4192 LP-4192 http://www bloodjournal org/content/128/22. ; 4192: abstract.
  14. Berdeja JG, Lin Y, Raje N, et al. Durable Clinical Responses in Heavily Pretreated Patients with Relapsed/Refractory Multiple Myeloma: Updated Results from a Multicenter Study of bb2121 Anti-Bcma CAR T Cell Therapy. Blood 2017;130():740 LP-740 http://www bloodjournal org/content/130/Suppl_1. ; 740(Suppl 1): abstract.
  15. Maher J. Immunotherapy of Malignant Disease Using Chimeric Antigen Receptor Engrafted T Cells. ISRN Oncology. 2012; 2012: 1–23.
  16. Hettle R, Corbett M, Hinde S, et al. The assessment and appraisal of regenerative medicines and cell therapy products: an exploration of methods for review, economic evaluation and appraisal. Health Technol Assess. 2017; 21(7): 1–204.
  17. Whittington M, McQueen R, Ollendorf D, et al. Long-term Survival and Value of Chimeric Antigen Receptor T-Cell Therapy for Pediatric Patients With Relapsed or Refractory Leukemia. JAMA Pediatrics. 2018; 172(12): 1161.
  18. Beatty GL, Haas AR, Maus MV, et al. Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies. Cancer Immunol Res. 2014; 2(2): 112–120.
  19. You F, Jiang L, Zhang B, et al. Phase 1 clinical trial demonstrated that MUC1 positive metastatic seminal vesicle cancer can be effectively eradicated by modified Anti-MUC1 chimeric antigen receptor transduced T cells. Sci China Life Sci. 2016; 59(4): 386–397.
  20. Ahmed N, Brawley VS, Hegde M, 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): 1688–1696.
  21. Sharpe M, Mount N. Genetically modified T cells in cancer therapy: opportunities and challenges. Disease Models & Mechanisms. 2015; 8(4): 337–350.
  22. Kakarla S, Gottschalk S. CAR T Cells for Solid Tumors. The Cancer Journal. 2014; 20(2): 151–155.
  23. Chen N, Morello A, Tano Z, et al. CAR T-cell intrinsic PD-1 checkpoint blockade: A two-in-one approach for solid tumor immunotherapy. OncoImmunology. 2017; 6(2): e1273302.
  24. Zhang C, Wang Z, Yang Z, et al. Phase I Escalating-Dose Trial of CAR-T Therapy Targeting CEA Metastatic Colorectal Cancers. Mol Ther. 2017; 25(5): 1248–1258.
  25. Zacharakis N, Chinnasamy H, Black M, et al. Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer. Nat Med. 2018; 24(6): 724–730.
  26. Zhang C, Oberoi P, Oelsner S, et al. Chimeric Antigen Receptor-Engineered NK-92 Cells: An Off-the-Shelf Cellular Therapeutic for Targeted Elimination of Cancer Cells and Induction of Protective Antitumor Immunity. Front Immunol. 2017; 8: 533.
  27. Tang X, Yang L, Li Z, et al. First-in-man clinical trial of CAR NK-92 cells: safety test of CD33-CAR NK-92 cells in patients with relapsed and refractory acute myeloid leukemia. Am J Cancer Res. 2018; 8(6): 1083–1089.
  28. Li Ye, Hermanson D, Moriarity B, et al. Human iPSC-Derived Natural Killer Cells Engineered with Chimeric Antigen Receptors Enhance Anti-tumor Activity. Cell Stem Cell. 2018; 23(2): 181–192.e5.
  29. Ruella M, Kenderian SS. Next-Generation Chimeric Antigen Receptor T-Cell Therapy: Going off the Shelf. BioDrugs. 2017; 31(6): 473–481.

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