Full Text (PDF)
Review Article

CAR-T Immunotherapy Against Cancer

Kinjal Upadhyay, Nisarg Kumar Teli

Author Information

Licence:

Attribution-Non-commercial 4.0 International (CC BY-NC 4.0)

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.


Indian Journal of Cancer Education and Research 12(2):p 63-73, July- Dec. 2024. | DOI: https://doi.org/10.21088/ijcer.2321.9815.12224.3

How Cite This Article:

Nisarg Kumar Teli, Kinjal Upadhyay. CAR-T Immunotherapy Against Cancer. Ind J Canc Educ Res 2024;12(2):63-73.

Timeline

Received : September 24, 2024         Accepted : November 12, 2024          Published : December 25, 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 supporting their approved use against acutely mphoblasticleukemia and largeb-celllymphomas. InternationalJournal of Molecular Sciences, 21(11),3906.
  • 3.   Barrett, D.M., Teachey, D.T., & Grupp, S.A. (2014). Toxicitymanagementforpatientsreceiving novelTcellengagingtherapies.Current opinion in pediatrics, 26(1),43.
  • 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 ofpharmacology, 625(1-3),41-54.
  • 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 EducationProgramBook,2012(1),143-151.
  • 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 immunology, 5,197.
  • 10.   Darby, S. C., Ewertz, M., McGale, P., Bennet, A. M., Blom-Goldman, U., Brønnum, D., ... & Hall, P. (2013). Risk of ischemic heart disease in women after radiotherapy for breast cancer. New England Journal of Medicine, 368(11), 987-998.
  • 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-Tcellsinflictsequentialkillingofmultipletumor targetcells. Cancerimmunologyresearch,3(5),483-494.
  • 13.   Davila, M. L., Riviere, I., Wang, X., Bartido, S., Park, J., Curran, K., ... & Brentjens, R. (2014).Effic acyandtoxicitymanagementof19-28zCARTcellthe rapyinBcellacutelymphoblasticleukemia. Science translationalmedicine, 6(224),224ra25-224ra25.
  • 14.   Dobosz, P., & Dzieciątkowski, T. (2019). The intriguing 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:potentialforcan cerimmunotherapy.In Springerseminarsinimmunop athology(Vol.18,No.2,pp.199-209). Springer-Verlag.
  • 18.   Fairweather,D.,&Cihakova,D.(2009).Alternativelya ctivatedmacrophagesininfectionandautoimmunity. Journalofautoimmunity,33(3-4),222-230.
  • 19.   Fan, J., Shang, D., Han, B., Song, J., Chen, H., & Yang, J. M. (2018). Adoptive cell transfer: is it ap romisingimmunotherapyforcolorectalcancer?. Theranostics, 8(20),5784
  • 20.   Feins, S., Kong, W., Williams, E. F., Milone, M. C., & Fraietta, J. A. (2019). An introduction tochimericantigenreceptor(CAR)T‐cellimmunothe rapyforhumancancer. Americanjournalofhematology, 94(S1),S3-S9.
  • 21.   Fukuhara,H.,Ino,Y.,& Todo, T. (2016).Oncolyticvirus therapy:A new era of cancertreatmentatdawn. Canc erscience,107(10),1373-1379.
  • 22.   G.(1999).Anti-tumoractivityofhumanTcellsexp ressingtheCC49-zetachimericimmunereceptor. Humangenetherapy,10(2),165-173.
  • 23.   Gasteiger, G., & Rudensky, A. Y. (2014). Interactions between innate and adaptive lymphocytes. NatureR eviewsImmunology,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 IL- 1blockade. Nature medicine,24(6),731-738.
  • 25.   Gonzalez, H., Hagerling, C., & Werb, Z. (2018). Roles of the immune system in cancer: from tumorinitiationtometastaticprogression. Genes&development,32(19-20), 1267-1284.
  • 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 chimericmolecules as functional receptors with antibody-type specificity. Proceedings of the National Academy ofSciences, 86(24),10024-10028.
  • 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.
  • 29.   Guo,C.,Manjili,M.H.,Subjeck, J.R.,Sarkar,D.,Fishe r,P.B.,&Wang,X. Y.(2013).Therapeuticcancervacci nes:past,present, andfuture.Advancesincancerresear ch,119,421-475.
  • 30.   H.(2012).Decade-longsafetyandfunctionofretrovir al-modifiedchimeric antigen receptor Tcells.Science translationalmedicine, 4(132),132ra53-132ra53.
  • 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 women, cancer and rehabilitation. Anthropology & Medicine, 14(1), 15-26.
  • 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 to couple to receptor-associatedsignaltransduction pathways. Cell, 64(5), 891-901.
  • 37.   Jin, K. T., Chen, B., Liu, Y. Y., Lan, H., & Yan, J. P. (2021). Monoclonal antibodies and chimericantigenreceptor (CAR)Tcells in the treatment of colorectal cancer. Cancercell international, 21(1),1-15
  • 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
  • 43.   Kochenderfer,J.N.,Wilson,W.H.,Janik,J.E.,Dudley, M.E.,Stetler-Stevenson,M.,Feldman,
  • 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.
  • 51.   Mcguinness, R.P., Ge,Y., Patel, S.D., Kashmiri, S.V., Lee, H.S., Hand, P.H., ... & Mcarthur, J.
  • 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. Y.(2017). Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. New EnglandJournalofMedicine,377(26),2531-2544.
  • 56.   Oiseth, S. J., & Aziz, M. S. (2017). Cancer immunotherapy: a brief review of the history, possibilities, andchallengesahead.JournalofCancerM etastasisandTreatment,3, 250-261.
  • 57.   Pardoll, D. M. (2012). The blockade of immune checkpoints in cancer immunotherapy. Nature ReviewsCancer, 12(4),252-264.
  • 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– modified Tcellsinchronic lymphoid leukemia. NengljMed,365, 725-733.
  • 60.   Porter, D.L.,Levine, B.L.,Kalos,M.,Bagg,A.,& June,C.H.(2011). Chimericantigenreceptor– modified Tcellsinchroniclymphoid leukemia. NengljMed, 365,725-733.
  • 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 forcancertherapy.Expert opiniononbiological therapy,11(7),855-873.
  • 63.   Rezvani,K.(2019).Adoptivecelltherapyusingengi neerednaturalkillercells. Bonemarrowtransplantati on,54(2),785-788.
  • 64.   Ruella, M., & Kalos, M. (2014). Adoptive immunotherapy for cancer. Immunological reviews, 257(1), 14-38.
  • 65.   Ruf,P.,&Lindhofer,H.(2001).Inductionofalong-lasti ngantitumorimmunitybyatrifunctionalbispecifican tibody. Blood,TheJournal oftheAmerican SocietyofHem atology,98(8),2526-2534.
  • 66.   S. A., ... & Rosenberg, S. A. (2010). Eradication of B-lineage cells and regression of lymphoma in a patienttreatedwith autologousTcells genetically engineered to recognize CD19. Blood, The Journal of theAmerican Society of Hematology,116(20),4099-4102.
  • 67.   Sadelain, M., Brentjens, R., & Rivière, I. (2013). The basic principles of chimeric antigen receptordesign. Cancerdiscovery,3(4),388-398.
  • 68.   Schirrmacher, V. (2019). From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment. International journal of oncology, 54(2), 407-419.
  • 69.   Scholler,J.,Brady,T.L.,Binder-Scholl,G.,Hwang,W.T .,Plesa,G.,Hege,K.M.,...&June,C.
  • 70.   Skorka, K., Ostapinska, K., Malesa, A., & Giannopoulos, K. (2020). The application of CARTcellsinhaematological malignancies.ArchivumImm unologiaeetTherapiaeExperimentalis,68(6),1-19.
  • 71.   Smyth, M. J., & Teng, M. W. (2018). 2018 Nobel Prize in physiology or medicine. Clinical & translationalimmunology,7(10).
  • 72.   Soltantoyeh, T., Akbari, B., Karimi, A., Mahmoodi Chalbatani, G., Ghahri-Saremi, N., Hadjati, J., ... &Mirzaei, H.R. (2021). Chimericantigenreceptor (CAR) Tcell therapy formetastaticmelanoma: challenges and road ahead. Cells, 10(6), 1450.
  • 73.   Southam, C.M., Brunschwig, A., Levin, A.G., & Dizon, Q.S. (1966).
  • 74.   ectofleukocytesontransplantabilityofhumancancer. Cancer, 19(11),1743-1753.
  • 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). Antibody-basedimmunotherapyofcancer. Cell,148(6),1081-1084.
  • 83.   Wilson,C.B.,Rowell,E.,&Sekimata,M.(2009). EpigeneticcontrolofT-helper-celldifferentiation. Nature reviewsimmunology,9(2),91-105.
  • 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

All authors contributed significantly to the work and approve its publication.

Ethics Declaration

This article does not involve any human or animal subjects, and therefore does not require ethics approval.

Acknowledgements

We are grateful to Dr. Sudeshna Menon (Head of the Department of Biochemistry and Biotechnology, St. Xavier’s College Autonomous, Ahmedabad) for providing this opportunity to accomplish by providing us with all kinds of support and resources required for our work.

Conflicts of Interest

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.


Licence:

Attribution-Non-commercial 4.0 International (CC BY-NC 4.0)

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.


Received Accepted Published
September 24, 2024 November 12, 2024 December 25, 2024

DOI: https://doi.org/10.21088/ijcer.2321.9815.12224.3

Keywords

ImmunotherapyCancerImmune systemCytokineAntibodyImmunoeditingImmunosurveillanceCancer immunotherapyAntigensReceptors

Article Level Metrics

Last Updated

Thursday 29 October 2026, 12:30:22 (IST)


2215

Accesses

3
331
00

Citations


NA
NA
NA

Download citation


Article Keywords


Keyword Highlighting

Highlight selected keywords in the article text.


Timeline


Received September 24, 2024
Accepted November 12, 2024
Published December 25, 2024

licence


Attribution-Non-commercial 4.0 International (CC BY-NC 4.0)

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.


Access this article



Share