CAR-T Immunotherapy in oncological treatment: literature review

Authors

DOI:

https://doi.org/10.33448/rsd-v11i4.27709

Keywords:

Neoplasms; Adoptive Immunotherapy; Chimeric Antigen Receptors; Lymphocytes; Immune system.

Abstract

Introduction: Immunotherapies are developed to overcome limitations of conventional cancer therapy through stimulating innate immune response against tumor antigen. Objective: Elaborate a review on CAR-T Immunotherapy (Chimeric T Cell Antigen Receptor) in cancer treatment. Methods: Bibliographic survey of systematic reviews published in PubMed in the last 5 years. Results: 21 studies were selected. Antitumor effect occurs through cell lysis, due to CAR-T lymphocytes release of cytokines. Tumor escape is related to tumor's ability to not expose its Major Histocompatibility Complex (MHC) and/or inability of the adaptive immune system to recognize tumor antigens. These molecular targets may be proteins, carbohydrates, or glycolipids, with CD19 standing out as target of this therapy and in neoplasms as leukemia and lymphoma. Four generations of CARs have been described, which differ in terms of co-stimulatory domains and consequent functional efficiency. The therapy is indicated for cases of recurrence/refractoriness of hematological neoplasms, however applicability in solid tumors has been studied. Adverse events of CAR-T immunotherapy described were: cytokine release syndrome, neurotoxicity, anaphylactic shock, autoimmune reactions, B cell aplasia, tumor lysis syndrome and graft-versus-host disease. Conclusions: CAR-T immunotherapy is a promising therapy against relapsed/refractory cancer. It’s mainly used in leukemias and lymphomas. Choice of dose and generation of CARs should be cautious, considering specific molecular targets of each neoplasm and its presence in healthy tissues, avoiding adverse events.

References

Almeida VL., Leitão A., Reina LCB, Montanari CA, Donnici CL; Lopes MTP. Cancer and cell cicle-specific and cell cicle nonspecific anticancer DNA-interactive agents: an introduction. Quím Nova. 2005; 28(1):118-129

Anwer, F., Shaukat, A. A., Zahid, U., Husnain, M., McBride, A., Persky, D., Lim, M., Hasan, N., & Riaz, I. B. (2017). Donor origin CAR T cells: graft versus malignancy effect without GVHD, a systematic review. Immunotherapy, 9(2), 123–130. https://doi.org/10.2217/imt-2016-0127

Cao, G., Lei, L., & Zhu, X. (2019). Efficiency and safety of autologous chimeric antigen receptor T-cells therapy used for patients with lymphoma: A systematic review and meta-analysis. Medicine, 98(42), e17506. https://doi.org/10.1097/MD.0000000000017506

Cao, J. X., Gao, W. J., You, J., Wu, L. H., Liu, J. L., & Wang, Z. X. (2019). The efficacy of anti-CD19 chimeric antigen receptor T cells for B-cell malignancies. Cytotherapy, 21(7), 769–781. https://doi.org/10.1016/j.jcyt.2019.04.005

Dammeijer, F., Lievense, L. A., Veerman, G. D., Hoogsteden, H. C., Hegmans, J. P., Arends, L. R., & Aerts, J. G. (2016). Efficacy of Tumor Vaccines and Cellular Immunotherapies in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 34(26), 3204–3212. https://doi.org/10.1200/JCO.2015.66.3955

Drokow, E. K., Ahmed, H., Amponsem-Boateng, C., Akpabla, G. S., Song, J., Shi, M., & Sun, K. (2019). Survival outcomes and efficacy of autologous CD19 chimeric antigen receptor-T cell therapy in the patient with diagnosed hematological malignancies: a systematic review and meta-analysis. Therapeutics and clinical risk management, 15, 637–646. https://doi.org/10.2147/TCRM.S203822

Grigor EJM, Fergusson D, Kekre N, Montroy J, Atkins H, Seftel MD, et al. Risks and benefits of chimeric antigen receptor T-Cell (CAR-T) therapy in cancer: a systematic review and meta-Analysis. Transfus Med Rev. 2019 Apr;33(2):98-110.

Hao, L., Li, T., Chang, L. J., & Chen, X. (2019). Adoptive Immunotherapy for B-cell Malignancies Using CD19- Targeted Chimeric Antigen Receptor T-Cells: A Systematic Review of Efficacy and Safety. Current medicinal chemistry, 26(17), 3068–3079. https://doi.org/10.2174/0929867324666170801101842

Holzinger, A., Barden, M., & Abken, H. (2016). The growing world of CAR T cell trials: a systematic review. Cancer immunology, immunotherapy : CII, 65(12), 1433–1450. https://doi.org/10.1007/s00262-016-1895-5

Jin, Z., Xiang, R., Qing, K., Li, X., Zhang, Y., Wang, L., Zhu, H., Mao, Y., Xu, Z., & Li, J. (2018). The severe cytokine release syndrome in phase I trials of CD19-CAR-T cell therapy: a systematic review. Annals of hematology, 97(8), 1327–1335. https://doi.org/10.1007/s00277-018-3368-8

Knudson AG. Antioncogenes and human cancer. Proc Natl Acad Sci USA. 1993;90(23):10914-10921.

Li, J., Wu, Z., & Zhao, N. (2019). Individual Patient Data Meta-Analysis from 16 Trials for Safety Factors in Cytokine Release Syndrome After CAR-T Therapy in Patients with Non-Hodgkin Lymphoma (NHL) and Acute Lymphoblastic Leukemia. Advances in therapy, 36(10), 2881–2894. https://doi.org/10.1007/s12325-019-01056-8

Maus MV, Fraietta JA, Levine BL, Kalos M, Zhao Y, June CH. Adoptive immunotherapy for cancer or viruses. Annu Rev Immunol. 2014;32:189-225.

Nagle, K., Tafuto, B., Palladino Kim, L., & Parrott, J. S. (2018). Effect of transplant status in CD19-targeted CAR T-cell therapy: a systematic review and meta-analysis. Medical oncology (Northwood, London, England), 35(11), 144. https://doi.org/10.1007/s12032-018-1204-6

Oppermann CP. Entendendo o câncer. 1 ed. Porto Alegre: Artmed; 2014.

Petrou P. (2019). Is it a Chimera? A systematic review of the economic evaluations of CAR-T cell therapy. Expert review of pharmacoeconomics & outcomes research, 19(5), 529–536. https://doi.org/10.1080/14737167.2019.1651646

Pettitt D, Arshad Z, Smith J, Stanic T, Holländer G, Brindley D. CAR-T cells: a systematic review and mixed methods analysis of the clinical trial landscape. Mol Ther. 2018 Feb 7;26(2):342-353.

Riaz, I. B., Zahid, U., Kamal, M. U., Husnain, M., McBride, A., Hua, A., Hamadani, A. A., George, L., Zeeshan, A., Sipra, Q. R., Raina, A., Rahman, B., Puvvada, S., & Anwer, F. (2017). Anti-CD 19 and anti-CD 20 CAR-modified T cells for B-cell malignancies: a systematic review and meta-analysis. Immunotherapy, 9(12), 979–993. https://doi.org/10.2217/imt-2017-0062

Sahlolbei, M., Dehghani, M., Kheiri Yeghane Azar, B., Vafaei, S., Roviello, G., D'Angelo, A., Madjd, Z., & Kiani, J. (2020). Evaluation of targetable biomarkers for chimeric antigen receptor T-cell (CAR-T) in the treatment of pancreatic cancer: a systematic review and meta-analysis of preclinical studies. International reviews of immunology, 39(5), 223–232. https://doi.org/10.1080/08830185.2020.1776274

Shah NN, Fry TJ. Mechanisms of resistance to CAR T cell therapy. Nat Rev Clin Oncol 16, 372–385 (2019).

Sohail, A., Mushtaq, A., Iftikhar, A., Warraich, Z., Kurtin, S. E., Tenneti, P., McBride, A., & Anwer, F. (2018). Emerging immune targets for the treatment of multiple myeloma. Immunotherapy, 10(4), 265–282. https://doi.org/10.2217/imt-2017-0136

Werle CH. Avaliação do efeito terapêutico em tumores murinos de cepas atenuadas de Salmonella enterica typhimurium. [Dissertação]. Campinas: Universidade Estadual de Campinas; 2016.

WHO, World Health Organization. (2021). Cancer https://www.who.int/news-room/fact-sheets/detail/cancer

Zeng, Y., Ruan, W., He, J., Zhang, J., Liang, W., Chen, Y., He, Q., & He, J. (2016). Adoptive Immunotherapy in Postoperative Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. PloS one, 11(9), e0162630. https://doi.org/10.1371/journal.pone.0162630

Zhang J, Wang L. The emerging world of TCR-T cell trials against cancer: a systematic review. Technol Cancer Res Treat. 2019 Jan 1;18:1533033819831068.

Zhao, B., Zhang, W., Yu, D., Xu, J., & Wei, Y. (2017). Adoptive immunotherapy shows encouraging benefit on non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget, 8(68), 113105–113119. https://doi.org/10.18632/oncotarget.19373

Zhu, J., Li, R., Tiselius, E., Roudi, R., Teghararian, O., Suo, C., & Song, H. (2017). Immunotherapy (excluding checkpoint inhibitors) for stage I to III non-small cell lung cancer treated with surgery or radiotherapy with curative intent. The Cochrane database of systematic reviews, 12(12), CD011300. https://doi.org/10.1002/14651858.CD011300.pub2

Zhu, Y., Tan, Y., Ou, R., Zhong, Q., Zheng, L., Du, Y., Zhang, Q., & Huang, J. (2016). Anti-CD19 chimeric antigen receptor-modified T cells for B-cell malignancies: a systematic review of efficacy and safety in clinical trials. European journal of haematology, 96(4), 389–396. https://doi.org/10.1111/ejh.12602

Downloads

Published

28/03/2022

How to Cite

AZZAM, G. B. .; OLIVEIRA, E. G. de .; AZZAM, R. S. .; MENEZES-RODRIGUES, F. S. . CAR-T Immunotherapy in oncological treatment: literature review. Research, Society and Development, [S. l.], v. 11, n. 4, p. e57411427709, 2022. DOI: 10.33448/rsd-v11i4.27709. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/27709. Acesso em: 12 nov. 2024.

Issue

Section

Health Sciences