This license enables
reusers to distribute, remix, adapt, and build upon the material in any medium
or format for noncommercial purposes only, and only so long as attribution is
given to the creator.
Nisarg Kumar Teli, Kinjal Upadhyay. CAR-T Immunotherapy Against Cancer. Ind J Canc Educ Res 2024;12(2):63-73
Timeline
Received : July 01, 2024
Accepted : July 15, 2024
Published : August 01, 2024
Abstract
Treatments like chemotherapy for cancer have less efficiency and specificity than required; immunotherapy provides one of the best means to have specific and more efficient treatment. With the great advancement in molecular biology, immunology, and cancer biology specific treatments like CAR-T immunotherapy have been introduced. Out of the various cancer immunotherapies discussed here, CAR-T immunotherapy provides the most promising results against certain cancers. CAR-T therapy has been discussed in detail with fundamental discussions of the immune system’s role in cancer and cancer immunotherapy. CAR-T immunotherapy a version of adoptive cell transfer therapy has given outstanding results that were beyond expectations. Some of them are discussed with minute details on CAR-T immunnnotherapy in this paper.
References
1. Abate-Daga, D., & Davila, M. L. (2016). CAR models: next-generation CAR modifications forenhanced T-cellfunction. Molecular Therapy-Oncolytics, 3, 16014.
2. Ahmad, A., Uddin, S., & Steinhoff,M.(2020). Cartcelltherapies: An overview of clinical studies
4. Bell, J. C., Lichty, B., & Stojdl, D. (2003). Getting oncolyticvirus therapies off theground. Cancercell, 4(1), 7-11.
5. Berraondo, P., Sanmamed, M. F., Ochoa, M. C., Etxeberria, I., Aznar, M. A., PérezGracia, J. L., ... & Melero, I. (2019). Cytokinesinclinicalcancerimmunotherapy.British journalofcancer,120(1),6-15.
6. Borghaei, H., Smith, M. R., & Campbell, K. S. (2009). Immunotherapy of cancer. European journal
7. Brentjens, R. J., & Curran, K. J. (2012). Novel cellular therapies for leukemia: CAR-modified Tcells targeted to the CD19 antigen. Hematology 2010, the American Society of Hematology
8. Brentjens, R., Yeh, R., Bernal, Y., Riviere, I., & Sadelain, M. (2010). Treatment of chroniclymphocytic leukemia with genetically targeted autologous T cells: case report of an unforeseen adverseevent ina phaseIclinicaltrial.MolecularTherapy,18(4),666-668.
9. Corthay, A. (2014). Does the immune system naturally protect against cancer?. Frontiers in
10. Darby, S. C., Ewertz, M., McGale, P., Bennet, A. M., Blom-Goldman, U., Brønnum, D., ... & Hall,
11. Darvin, P., Toor, S. M., Sasidharan Nair, V., & Elkord, E. (2018). Immune checkpoint inhibitors: recent progress and potential biomarkers.Experimental & molecular medicine, 50(12),1-11.
12. Davenport, A. J., Jenkins, M. R., Cross, R. S., Yong, C. S., Prince, H. M., Ritchie, D. S., ... &Neeson,P.J.(2015).CAR-Tcellsinflictsequentialkillingofmultipletumortargetcells. Cancerimmunologyresearch,3(5),483-494.
13. Davila, M. L., Riviere, I., Wang, X., Bartido, S., Park, J., Curran, K., ... & Brentjens, R. (2014).Efficacyandtoxicitymanagementof19-28zCARTcelltherapyinBcellacutelymphoblasticleukemia. Science translationalmedicine, 6(224),224ra25-224ra25.
14. Dobosz, P., &Dzieciątkowski, T. (2019). Theintriguing history of cancer immunotherapy. Frontiers inimmunology,2965.
15. Dunn, G. P., Old, L. J., & Schreiber, R. D. (2004). The immunobiology of cancer immunosurveillance andimmunoediting. Immunity,21(2),137-148.
16. Eggermont, L. J., Paulis, L. E., Tel, J., & Figdor, C. G. (2014). Towards efficient cancer immunotherapy: advances in developing artificial antigen-presenting cells. Trends in biotechnology, 32(9), 456-465
17. Eshhar, Z., Bach, N., Fitzer-Attas, C. J., Grosse, G., Lustgarten, J., Waks, T., & Schindler, D. G.(1996,June).TheT-bodyapproach:potentialforcancerimmunotherapy.In Springerseminarsinimmunopathology(Vol.18,No.2,pp.199-209). Springer-Verlag.
19. Fan, J., Shang, D., Han, B., Song, J., Chen, H., & Yang, J. M. (2018). Adoptive cell transfer: is it apromisingimmunotherapyforcolorectalcancer?.Theranostics, 8(20),5784
20. Feins, S., Kong, W., Williams, E. F., Milone, M. C., & Fraietta, J. A. (2019). An introduction tochimericantigenreceptor(CAR)T cellimmunotherapyforhumancancer. Americanjournalofhematology,94(S1),S3-S9.
21. Fukuhara,H.,Ino,Y.,& Todo, T. (2016).Oncolyticvirus therapy:A new era of cancertreatmentatdawn. Cancerscience,107(10),1373-1379.
23. Gasteiger, G., & Rudensky, A. Y. (2014). Interactions between innate and adaptive lymphocytes. NatureReviewsImmunology,14(9),631-639.
24. Giavridis, T., van derStegen, S. J.,Eyquem, J., Hamieh, M., Piersigilli,A.,& Sadelain,M.(2018). CAR T cell–induced cytokine release syndrome is mediated by macrophages and abated by IL1blockade. Nature medicine,24(6),731-738.
25. Gonzalez, H., Hagerling, C., & Werb, Z. (2018). Roles of the immune system in cancer:
26. Graham, C., Hewitson, R., Pagliuca, A., & Benjamin, R. (2018). Cancer immunotherapy withCAR-Tcells–beholdthe future.ClinicalMedicine,18(4),324.
27. Gross, G., Waks, T., & Eshhar, Z. (1989). Expression of immunoglobulin-T-cell receptor
28. Grupp, S. A., Kalos, M., Barrett, D., Aplenc, R., Porter, D. L., Rheingold, S. R., ... & June, C. H.(2013). Chimeric antigen receptor–modified T cells for acute lymphoid leukemia. New England Journal ofMedicine, 368(16),1509-1518.
31. H a a n e n , J . B . , & R o b e r t , C . ( 2 0 1 5 ) . I m m u n e c h e c k p o i n t i n h i b i t o r s . I m m u n o -Oncology,42,55-66.
32. Hadden,J.W.(2003).Immunodeficiencyandcancer:p rospectsforcorrection. International immunopharmac ology,3(8),1061-1071.
33. Hansen, H. P. (2007). Hair loss induced by chemotherapy: An anthropological study of
34. Hao, N. B., Lü, M. H., Fan, Y. H., Cao, Y. L., Zhang, Z. R., & Yang, S. M. (2012). Macrophages in tumor micro environments and the progress ion of tumors. Clinical and Developmental Immunology, 2012.
35. Hinrichs, C. S., & Rosenberg, S. A. (2014). Exploiting the curative potential of adoptive T-cell therapy forcancer. Immunological reviews, 257(1),56-71.
36. Irving, B. A., & Weiss, A. (1991). The cytoplasmic domain of the T cell receptor ζ chain is sufficient
37. Jin, K. T., Chen, B., Liu, Y. Y., Lan, H., & Yan, J. P. (2021). Monoclonal antibodies and
38. June, C.H. (2007). Principles of adoptive T cell cancer therapy. The Journal of clinical investigation, 117(5), 1204-1212.
39. June, C. H., & Sadelain, M. (2018). Chimeric antigen receptor therapy. New England Journal of Medicine, 379(1),64-73.
40. June, C. H., Maus, M. V., Plesa, G., Johnson, L. A., Zhao, Y., Levine, B. L., ... & Porter, D. L. (2014).Engineered Tcellsfor cancer therapy. Cancer Immunology, Immunotherapy, 63(9), 969-975.
41. June, C. H., O’Connor, R. S., Kawalekar, O. U., Ghassemi, S., & Milone, M. C. (2018). CAR T cellimmunotherapyforhumancancer.Science, 359(6382),1361-1365.
42. Kalos, M., Levine, B. L., Porter, D. L., Katz, S., Grupp, S. A., Bagg, A., & June, C. H. (2011). Tcells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Science translational medicine, 3(95), 95ra73-95ra73
44. Lakshmi Narendra, B., Eshvendar Reddy, K., Shantikumar, S., & Ramakrishna, S. (2013). Immune system:adouble-edgedswordincancer.Inflammation Research,62(9), 823-834.
45. Langers, I., Renoux, V. M., Thiry, M., Delvenne, P., & Jacobs, N. (2012). Natural killer cells: role in local tumor growth and metastasis. Biologics: targets & therapy, 6,73.
46. Lee, D. W., Gardner, R., Porter, D. L., Louis, C. U., Ahmed, N., Jensen, M., ... & Mackall, C. L.(2014). Current concepts in the diagnosis andmanagement of cytokine release syndrome. Blood, The Journal of the American Society of Hematology, 124(2), 188-195.
47. Louis, C.U., Savoldo, B., Dotti, G., Pule, M., Yvon, E., Myers, G.D., ... & Brenner, M.K. (2011). Antitumor activity and long-term fate of chimeric antigen receptor–positive T cells in patients with neuroblastoma. Blood, The Journal of the American Society of Hematology, 118(23), 6050-6056.
48. Mantovani, A., Sica, A., Sozzani, S., Allavena, P., Vecchi, A., & Locati, M. (2004). The chemokine systemindiverseforms of macrophageactivationand polarization.Trendsin immunology,25(12),677-686.
49. Marcus, A., & Eshhar, Z. (2011). Allogeneic adoptive cell transfer therapy as a potent universal treatmentfor cancer.Oncotarget,2(7),525.
50. McCarthy, E.F. (2006). Thetoxins of WilliamB.Coley and the treatment of boneandsoft-tissuesarcomas. The Iowaorthopaedic journal, 26,154.
52. Mitchison, N.A.(1955). Studies on the immunological response toforeign tumor transplants in the mouse:
53. Mohanty, R., Chowdhury, C. R., Arega, S., Sen, P., Ganguly, P., & Ganguly, N. (2019). CAR Tcelltherapy:A new era for cancer treatment.Oncologyreports, 42 (6), 2183-2195.
54. Morrow, G. R., & Dobkin, P. L. (1988). Anticipatory nausea and vomiting in cancer patients undergoing chemotherapy treatment: Prevalence, etiology, and behavioral interventions. Clinical Psychology Review, 8(5), 517-556.
55. Neelapu, S. S., Locke, F. L., Bartlett, N. L., Lekakis, L. J., Miklos, D. B., Jacobson, C. A., ... & Go, W.
56. Oiseth, S. J., & Aziz, M. S. (2017). Cancer immunotherapy: a brief review of the history,
57. Pardoll, D. M. (2012). The blockade of immune checkpoints in cancer immunotherapy. Nature
58. Park, J. H., & Brentjens, R. J. (2015). Are all chimeric antigen receptors created equal?. Journal ofClinicalO ncology:OfficialJournaloftheAmericanSocietyof Clinical Oncology,33(6),651-653.
59. Porter, D. L., Levine, B. L., Kalos, M., Bagg, A., & June, C. H. (2011). Chimeric antigen receptor–
61. Pylayeva-Gupta, Y., Das, S., Handler, J. S., Hajdu, C. H., Coffre, M., Koralov, S. B., & Bar-Sagi, D.(2016). IL35-producing B cells promote the development of pancreatic neoplasia. Cancer discovery, 6(3),247-255.
62. Ramos, C. A., & Dotti, G. (2011). Chimeric antigen receptor (CAR)-engineered lymphocytes
70. Skorka, K., Ostapinska, K., Malesa, A., & Giannopoulos, K. (2020). The application of CARTcellsinhaematological malignancies.ArchivumImmunologiaeetTherapiaeExperimentalis,68(6),1-19.
71. Smyth, M. J., & Teng, M. W. (2018). 2018 Nobel Prize in physiology or medicine. Clinical & translationalimmunology,7(10).
75. Spear, T. T., Nagato, K., & Nishimura, M. I. (2016). Strategies to genetically engineer T cells for cancerimmunotherapy. CancerImmunology,Immunotherapy,65(6),631-649.
76. Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 71(3), 209-249.
77. Taylor, C. W., & Kirby, A. M. (2015). Cardiac sideeffects from breast cancer radiotherapy. Clinical Oncology, 27(11), 621-629.
78. The role of lymph node cells in conferring immunity by adoptive transfer. The Journal of experimentalmedicine, 102(2),157-177.
79. Vesely, M. D., Kershaw, M. H., Schreiber, R. D., & Smyth, M. J. (2011). Natural innate and adaptiveimmunitytocancer.Annualreview ofimmunology,29, 235-271.
80. Waldman,A.D.,Fritz,J.M.,&Lenardo,M.J.(2020).
81. idetocancerimmunotherapy: from Tcell basic science to clinical practice. Nature Reviews Immunology, 20(11), 651-668.
82. Weiner,L.M.,Murray,J.C.,&Shuptrine,C.W.(2012).An t ibo dy- base di mm u n oth era pyo fc an cer . Cell,148(6),1081-1084.
84. Zang, X. (2018). 2018 Nobel Prize in medicine awarded to cancer immunotherapy: Immune checkpointblockade–Apersonal account.Genes&diseases, 5(4),302.
Data Sharing Statement
There are no additional data available. All raw data and code are available upon request
Funding
This research received no funding.
Author Contributions
Whether all authors contributed significantly to the work and approve its publication.
Ethics Declaration
Provide information related to the Ethics Committee approval with approval number OR write "This article does not involve any human or animal subjects, and therefore does not require ethics approval.
Acknowledgements
We would like to express our gratitude to the patients, their families, and all those who have contributed to this study.
Conflicts of Interest
The authors report no conflicts of interest in this work.
About this article
Cite this article
Nisarg Kumar Teli, Kinjal Upadhyay. CAR-T Immunotherapy Against Cancer. Ind J Canc Educ Res 2024;12(2):63-73
This license enables
reusers to distribute, remix, adapt, and build upon the material in any medium
or format for noncommercial purposes only, and only so long as attribution is
given to the creator.
This license enables
reusers to distribute, remix, adapt, and build upon the material in any medium
or format for noncommercial purposes only, and only so long as attribution is
given to the creator.
Description: one of the most common CARs has the parts of both monoclonal antibodies and the TCR complex. The interaction of CARs with tumor antigens initiates the signal transduction to activate the T- cells.
Heading
Description: General structure of Chimeric Antigen Receptor. Adapted from (Skorka et al., 2020)
Heading
Description: Transgenic TCR and 3 generations of CARs. As per the figure it can be seen that the main difference between the
generations of CARs is the number of co-stimulatory domains and with the increase in the number of co-stimulatory
domains the efficiency and the range of CARs increase. Adapted from (June et al., 2018)
Heading
Description: CAR-T cells are injected into the bloodstream where these cells undergo extensive proliferation and then they travel to the location of the tumor. After reaching the tumor site, these cells recognize tumor antigens presented on tumor cells and will eliminate tumor cells. But the elimination of tumor cells will result in antigen release which will further activate immune response by antigen presentation. Adapted from (June & Sadelain, 2018)
Heading
Description: No description available.
Heading
Description: Different clinical trials for different cancers with different generations of CARs