CAR T CELL THERAPY
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Keywords
Abstract
CAR T cells refer to T lymphocytes that undergo genetic engineering to generate artificial T cell receptors, serving a crucial role in immunotherapy1. Chimeric antigen receptors (CARs) are specialized cell-surface receptors designed to identify specific proteins (antigens)2. These receptors, considered chimeric because they incorporate components from various receptors, are created by extracting T cells from the patient and modifying them in a laboratory setting3. The modified T cells then display chimeric antigen receptors, or CARs, on their surface.
References
1. Chen L, Qiao D, Wang J, Tian G, Wang M. Cancer immunotherapy with lymphocytes genetically engineered with T cell receptors for solid cancers. Immunology Letters. 2019 Dec 1;216:51-62.
2. Sadelain M, Brentjens R, Rivière I. The basic principles of chimeric antigen receptor design. Cancer discovery. 2013 Apr 1;3(4):388-98.
3. Maher J. Immunotherapy of malignant disease using chimeric antigen receptor engrafted T cells. International Scholarly Research Notices. 2012;2012.
4. Chang ZL, Chen YY. CARs: synthetic immunoreceptors for cancer therapy and beyond. Trends in molecular medicine. 2017 May 1;23(5):430-50.
5. Asmamaw Dejenie T, Tiruneh G/Medhin M, Dessie Terefe G, Tadele Admasu F, Wale Tesega W, Chekol Abebe E. Current updates on generations, approvals, and clinical trials of CAR T-cell therapy. Human Vaccines & Immunotherapeutics. 2022 Nov 30;18(6):2114254.
6. Steyn A. Transmembrane glycoprotein gp41 of the Human Immunodeficiency Virus Type I: gene synthesis, recombinant expression and immunological characterization. University of Pretoria (South Africa); 2011.
7. Zhang C, Liu J, Zhong JF, Zhang X. Engineering car-t cells. Biomarker research. 2017 Dec;5(1):1-6.
8. Jin J, Cheng J, Huang M, Luo H, Zhou J. Fueling chimeric antigen receptor T cells with cytokines. American journal of cancer research. 2020;10(12):4038.
9. Sievers NM, Dörrie J, Schaft N. CARs: beyond T cells and T cell-derived signaling domains. International Journal of Molecular Sciences. 2020 May 15;21(10):3525.
10. Lanitis E, Poussin M, Klattenhoff AW, Song D, Sandaltzopoulos R, June CH, Powell Jr DJ. Chimeric antigen receptor T Cells with dissociated signaling domains exhibit focused antitumor activity with reduced potential for toxicity in vivo. Cancer immunology research. 2013 Jul 1;1(1):43-53.
11. Honikel MM, Olejniczak SH. Co-stimulatory receptor signaling in CAR-T cells. Biomolecules. 2022 Sep 15;12(9):1303.
12. Subklewe M, von Bergwelt-Baildon M, Humpe A. Chimeric antigen receptor T cells: a race to revolutionize cancer therapy. Transfusion Medicine and Hemotherapy. 2019 Feb 5;46(1):15-24.
13. Chatterjee G, Dhende P, Raj S, Shetty V, Ghogale S, Deshpande N, Girase K, Patil J, Kalra A, Narula G, Dalvi K. 15‐color highly sensitive flow cytometry assay for post anti‐CD19 targeted therapy (anti‐CD19‐CAR‐T and blinatumomab) measurable residual disease assessment in B‐lymphoblastic leukemia/lymphoma: Real‐world applicability and challenges. European Journal of Haematology. 2024 Jan;112(1):122-36.
14. Liu J, Zhong JF, Zhang X, Zhang C. Allogeneic CD19-CAR-T cell infusion after allogeneic hematopoietic stem cell transplantation in B cell malignancies. Journal of hematology & oncology. 2017 Dec;10(1):1-8.
15. Spiegel JY, Patel S, Muffly L, Hossain NM, Oak J, Baird JH, Frank MJ, Shiraz P, Sahaf B, Craig J, Iglesias M. CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial. Nature medicine. 2021 Aug;27(8):1419-31.
16. Majzner RG, Mackall CL. Tumor antigen escape from CAR T-cell therapy. Cancer discovery. 2018 Oct 1;8(10):1219-26.
17. Careful antigen selection in CAR design is essential to ensure therapeutic effectiveness and minimize "on-target off-tumor" toxicity
18. Hong M, Talluri S, Chen YY. Advances in promoting chimeric antigen receptor T cell trafficking and infiltration of solid tumors. Current Opinion in Biotechnology. 2023 Dec 1;84:103020.
19. Haist M, Stege H, Grabbe S, Bros M. The functional crosstalk between myeloid-derived suppressor cells and regulatory T cells within the immunosuppressive tumor microenvironment. Cancers. 2021 Jan 8;13(2):210.
20. Yang C, Nguyen J, Yen Y. Complete spectrum of adverse events associated with chimeric antigen receptor (CAR)-T cell therapies. Journal of Biomedical Science. 2023 Oct 21;30(1):89.
21. Sterner RC, Sterner RM. CAR-T cell therapy: current limitations and potential strategies. Blood cancer journal. 2021 Apr 6;11(4):69.
22. De Bousser E, Callewaert N, Festjens N. T cell engaging immunotherapies, highlighting chimeric antigen receptor (CAR) T cell therapy. Cancers. 2021 Dec 1;13(23):6067.
23. Watanabe K, Kuramitsu S, Posey Jr AD, June CH. Expanding the therapeutic window for CAR T cell therapy in solid tumors: the knowns and unknowns of CAR T cell biology. Frontiers in immunology. 2018 Oct 26;9:2486.
24. Mohanty R, Chowdhury CR, Arega S, Sen P, Ganguly P, Ganguly N. CAR T cell therapy: A new era for cancer treatment. Oncology reports. 2019 Dec 1;42(6):2183-95.
25. Nguyen A, Johanning G, Shi Y. Emerging novel combined CAR-T cell therapies. Cancers. 2022 Mar 9;14(6):1403.
26. Hiltensperger M, Krackhardt AM. Current and future concepts for the generation and application of genetically engineered CAR-T and TCR-T cells. Frontiers in Immunology. 2023 Mar 6;14:1121030.
2. Sadelain M, Brentjens R, Rivière I. The basic principles of chimeric antigen receptor design. Cancer discovery. 2013 Apr 1;3(4):388-98.
3. Maher J. Immunotherapy of malignant disease using chimeric antigen receptor engrafted T cells. International Scholarly Research Notices. 2012;2012.
4. Chang ZL, Chen YY. CARs: synthetic immunoreceptors for cancer therapy and beyond. Trends in molecular medicine. 2017 May 1;23(5):430-50.
5. Asmamaw Dejenie T, Tiruneh G/Medhin M, Dessie Terefe G, Tadele Admasu F, Wale Tesega W, Chekol Abebe E. Current updates on generations, approvals, and clinical trials of CAR T-cell therapy. Human Vaccines & Immunotherapeutics. 2022 Nov 30;18(6):2114254.
6. Steyn A. Transmembrane glycoprotein gp41 of the Human Immunodeficiency Virus Type I: gene synthesis, recombinant expression and immunological characterization. University of Pretoria (South Africa); 2011.
7. Zhang C, Liu J, Zhong JF, Zhang X. Engineering car-t cells. Biomarker research. 2017 Dec;5(1):1-6.
8. Jin J, Cheng J, Huang M, Luo H, Zhou J. Fueling chimeric antigen receptor T cells with cytokines. American journal of cancer research. 2020;10(12):4038.
9. Sievers NM, Dörrie J, Schaft N. CARs: beyond T cells and T cell-derived signaling domains. International Journal of Molecular Sciences. 2020 May 15;21(10):3525.
10. Lanitis E, Poussin M, Klattenhoff AW, Song D, Sandaltzopoulos R, June CH, Powell Jr DJ. Chimeric antigen receptor T Cells with dissociated signaling domains exhibit focused antitumor activity with reduced potential for toxicity in vivo. Cancer immunology research. 2013 Jul 1;1(1):43-53.
11. Honikel MM, Olejniczak SH. Co-stimulatory receptor signaling in CAR-T cells. Biomolecules. 2022 Sep 15;12(9):1303.
12. Subklewe M, von Bergwelt-Baildon M, Humpe A. Chimeric antigen receptor T cells: a race to revolutionize cancer therapy. Transfusion Medicine and Hemotherapy. 2019 Feb 5;46(1):15-24.
13. Chatterjee G, Dhende P, Raj S, Shetty V, Ghogale S, Deshpande N, Girase K, Patil J, Kalra A, Narula G, Dalvi K. 15‐color highly sensitive flow cytometry assay for post anti‐CD19 targeted therapy (anti‐CD19‐CAR‐T and blinatumomab) measurable residual disease assessment in B‐lymphoblastic leukemia/lymphoma: Real‐world applicability and challenges. European Journal of Haematology. 2024 Jan;112(1):122-36.
14. Liu J, Zhong JF, Zhang X, Zhang C. Allogeneic CD19-CAR-T cell infusion after allogeneic hematopoietic stem cell transplantation in B cell malignancies. Journal of hematology & oncology. 2017 Dec;10(1):1-8.
15. Spiegel JY, Patel S, Muffly L, Hossain NM, Oak J, Baird JH, Frank MJ, Shiraz P, Sahaf B, Craig J, Iglesias M. CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial. Nature medicine. 2021 Aug;27(8):1419-31.
16. Majzner RG, Mackall CL. Tumor antigen escape from CAR T-cell therapy. Cancer discovery. 2018 Oct 1;8(10):1219-26.
17. Careful antigen selection in CAR design is essential to ensure therapeutic effectiveness and minimize "on-target off-tumor" toxicity
18. Hong M, Talluri S, Chen YY. Advances in promoting chimeric antigen receptor T cell trafficking and infiltration of solid tumors. Current Opinion in Biotechnology. 2023 Dec 1;84:103020.
19. Haist M, Stege H, Grabbe S, Bros M. The functional crosstalk between myeloid-derived suppressor cells and regulatory T cells within the immunosuppressive tumor microenvironment. Cancers. 2021 Jan 8;13(2):210.
20. Yang C, Nguyen J, Yen Y. Complete spectrum of adverse events associated with chimeric antigen receptor (CAR)-T cell therapies. Journal of Biomedical Science. 2023 Oct 21;30(1):89.
21. Sterner RC, Sterner RM. CAR-T cell therapy: current limitations and potential strategies. Blood cancer journal. 2021 Apr 6;11(4):69.
22. De Bousser E, Callewaert N, Festjens N. T cell engaging immunotherapies, highlighting chimeric antigen receptor (CAR) T cell therapy. Cancers. 2021 Dec 1;13(23):6067.
23. Watanabe K, Kuramitsu S, Posey Jr AD, June CH. Expanding the therapeutic window for CAR T cell therapy in solid tumors: the knowns and unknowns of CAR T cell biology. Frontiers in immunology. 2018 Oct 26;9:2486.
24. Mohanty R, Chowdhury CR, Arega S, Sen P, Ganguly P, Ganguly N. CAR T cell therapy: A new era for cancer treatment. Oncology reports. 2019 Dec 1;42(6):2183-95.
25. Nguyen A, Johanning G, Shi Y. Emerging novel combined CAR-T cell therapies. Cancers. 2022 Mar 9;14(6):1403.
26. Hiltensperger M, Krackhardt AM. Current and future concepts for the generation and application of genetically engineered CAR-T and TCR-T cells. Frontiers in Immunology. 2023 Mar 6;14:1121030.
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Published
Mar 13, 2024
Article Details
How to Cite
Dr. Renuka, Dr. Juhi Aggarwal, & Dr. Eram H. Pasha. (2024). CAR T CELL THERAPY. Journal of Population Therapeutics and Clinical Pharmacology, 31(3), 595–600. https://doi.org/10.53555/jptcp.v31i3.4984
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All articles published in JPTCP are licensed under Copyright Creative Commons Attribution-NonCommercial 4.0 International License.
Author Biographies
Dr. Renuka
Post graduate student Department of Biochemistry, Santosh Medical College & Hospital
Dr. Juhi Aggarwal
Prof & Head of Department of Biochemistry
Dr. Eram H. Pasha
Assistant Professor Department of Biochemistry