Theoretical and Natural Science
- The Open Access Proceedings Series for Conferences
Proceedings of the International Conference on Modern Medicine and Global Health (ICMMGH 2023)
Series Vol. 6 , 03 August 2023
Open
Access | Article
Existing methods to improve immunotherapy's limitations: CAR-T cell therapy and checkpoint inhibitors
* Author to whom correspondence should be addressed.
Abstract
Immunotherapy is a form of treatment for cancer that works by provoking the immune system of the body into tracking down and destroying cancer cells. CAR-T-CT is a treatment that makes use of CAR-T cells (CARs), which are T cells (T-Cs) that have been modified in some way by the incorporation of engineered synthetic receptors. This therapy is designed to destroy cells that express a specific target antigen, and its primary objective is to do so by locating and killing those cells. Due to the fact that Immune CPI inhibits the production of specific proteins (checkpoint protein) on immune cells as well as on cancer cells thereby preventing the immune system from combating cancer, Immune CPI are used to treat cancer. By inhibiting the activity of these proteins, CPI is able to contribute to the process of stimulating the immune system to specifically target and destroy cancer cells. However, there are still some limitations that exist, and these have the potential to reduce the effectiveness of the treatment or produce some side effects that are life-threatening. This article makes a few suggestions for innovative steps that could be taken in order to both improve the current state of affairs and find answers to any problems that may arise in the near or distant future. The article makes these suggestions in order to improve the current state of affairs and find answers to any problems that may arise in the future.
Keywords
immunotherapy, CAR-T cell therapy, checkpoint inhibitors
References
1. Abbott M, Ustoyev Y. Cancer and the Immune System: The History and Background of Immunotherapy. Semin Oncol Nurs, 35(5):150923;2019
2. Riley RS, June CH, Langer R, Mitchell MJ. Delivery technologies for cancer immunotherapy. Nat Rev Drug Discov,18(3):175-196;2019
3. National Cancer Institute. Immune Checkpoint Inhibitors;2022.4.7; 2023.3.19; Immune Checkpoint Inhibitors - NCI (cancer.gov)
4. Mayo clinic. CAR-T Cell Therapy Program;2022.2.19;2023.3.19; CAR-T Cell Therapy Program - Department home - Mayo Clinic
5. Sterner, R.C., Sterner, R.M. CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J, 11, 69;2021
6. Majzner RG, Mackall CL. Tumor Antigen Escape from CAR T-cell Therapy. Cancer Discov, 8(10):1219-1226; 2018
7. American Cancer Society. CAR T-cell Therapy and Its Side Effects;2022.3.1; 2023.3.19; CAR T-cell Therapy and Its Side Effects (cancer.org)
8. Dobosz P, Stępień M, Golke A, Dzieciątkowski T. Challenges of the Immunotherapy: Perspectives and Limitations of the Immune Checkpoint Inhibitor Treatment. Int J Mol Sci,23(5):2847; 2022
9. American Cancer Society. Immune Checkpoint Inhibitors and Their Side Effects;2022.11.17; 2023.3.19; Immune Checkpoint Inhibitors and Their Side Effects (cancer.org)
10. Walsh, Z., Ross, S., & Fry, T. J. Multi-Specific CAR Targeting to Prevent Antigen Escape. Current Hematologic Malignancy Reports. (2019). Walsh Z, Ross S, Fry TJ. Multi-Specific CAR Targeting to Prevent Antigen Escape. Curr Hematol Malig Rep,14(5):451-459;2019
11. Dai H, Wu Z, Jia H, Tong C, Guo Y, Ti D, Han X, Liu Y, Zhang W, Wang C, Zhang Y, Chen M, Yang Q, Wang Y, Han W. Bispecific CAR-T cells targeting both CD19 and CD22 for therapy of adults with relapsed or refractory B cell acute lymphoblastic leukemia. J Hematol Oncol,13(1):30; 2020
12. Fisher J, Abramowski P, Wisidagamage Don ND, Flutter B, Capsomidis A, Cheung GW, Gustafsson K, Anderson J. Avoidance of On-Target Off-Tumor Activation Using a Co-stimulation-Only Chimeric Antigen Receptor. Mol Ther,25(5):1234-1247; 2017
13. Grosser, R., Cherkassky, L., Chintala, N., & Adusumilli, P. S. Combination Immunotherapy with CAR T Cells and Checkpoint Blockade for the Treatment of Solid Tumors. Cancer Cell, 36(5):471–482;2019
14. Kennedy, L. B., & Salama, A. K. S. A review of cancer immunotherapy toxicity. CA: A Cancer Journal for Clinicians, 70(2):86–104;2020
15. Shimabukuro-Vornhagen A, Gödel P, Subklewe M, Stemmler HJ, Schlößer HA, Schlaak M, Kochanek M, Böll B, von Bergwelt-Baildon MS. Cytokine release syndrome. J Immunother Cancer,6(1):56; 2018
16. Tormoen GW, Crittenden MR, Gough MJ. Role of the immunosuppressive microenvironment in immunotherapy. Adv Radiat Oncol, 3(4):520-526; 2018
17. Birbrair, A. (Ed.). Tumor Microenvironment. Advances in Experimental Medicine and Biology;2020
18. Hou AJ, Chen LC, Chen YY. Navigating CAR-T cells through the solid-tumour microenvironment. Nat Rev Drug Discov,20(7):531-550; 2021
19. Quach HT, Johnson DB, LeBoeuf NR, Zwerner JP, Dewan AK. Cutaneous adverse events caused by immune checkpoint inhibitors. J Am Acad Dermatol,85(4):956-966; 2021
20. Tian Y, Li Y, Shao Y, Zhang Y. Gene modification strategies for next-generation CAR T cells against solid cancers. J Hematol Oncol,13(1):54;2020
21. Seto T, Sam D, Pan M. Mechanisms of Primary and Secondary Resistance to Immune Checkpoint Inhibitors in Cancer. Med Sci (Basel), 7(2):14;201
22. Schoenfeld, A. J., & Hellmann, M. D. Acquired Resistance to Immune Checkpoint Inhibitors. Cancer Cell, 37(4):443–455;2020
23. Conroy, M., Naidoo, J. Immune-related adverse events and the balancing act of immunotherapy. Nat Commun 13:392 ;2022
24. von Itzstein MS, Khan S, Gerber DE. Investigational Biomarkers for Checkpoint Inhibitor Immune-Related Adverse Event Prediction and Diagnosis. Clin Chem,66(6):779-793;2020
25. Hou A, Hou K, Huang Q, Lei Y, Chen W. Targeting Myeloid-Derived Suppressor Cell, a Promising Strategy to Overcome Resistance to Immune Checkpoint Inhibitors. Front Immunol, 11:783;2020
Data Availability
The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License. Authors who publish this series agree to the following terms:
1. Authors retain copyright and grant the series right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this series.
2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the series's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this series.
3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See Open Access Instruction).
- Volume Title
- Proceedings of the International Conference on Modern Medicine and Global Health (ICMMGH 2023)
- ISBN (Print)
- 978-1-915371-65-2
- ISBN (Online)
- 978-1-915371-66-9
- Published Date
- 03 August 2023
- Series
- Theoretical and Natural Science
- ISSN (Print)
- 2753-8818
- ISSN (Online)
- 2753-8826
- DOI
- 10.54254/2753-8818/6/20230249
- Copyright
- © 2023 The Author(s)
- Open Access
- This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited