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Enhanced chimeric antigen receptor T cell therapy through co‐application of synergistic combination partners.
Biomedicines 10:307 (2022)
Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable response rates and revolutionized the treatment of patients suffering from defined hematological malignancies. However, many patients still do not respond to this therapy or relapse after an initial remission, underscoring the need for improved efficacy. Insufficient in vivo activity, persistence, trafficking, and tumor infiltration of CAR T cells, as well as antigen escape and treatment‐associated adverse events, limit the therapeutic success. Multiple strategies and approaches have been investigated to further improve CAR T cell therapy. Besides genetic modification of the CAR itself, the combination with other treatment modalities has the potential to improve this approach. In particular, combining CAR T cells with clinically approved compounds such as monoclonal antibodies and small molecule inhibitors might be a promising strategy. Combination partners could already be applied during the production process to influence the cellular composition and immunophenotype of the final CAR T cell product. Alternatively, simultaneous administration of clinically approved compounds with CAR T cells would be another feasible avenue. In this review, we will discuss current strategies to combine CAR T cells with compounds to overcome recent limitations and further enhance this promising cancer therapy, potentially broadening its application beyond hematology.
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Publication type
Article: Journal article
Document type
Review
Keywords
Adoptive T Cell Therapy ; Chimeric Antigen Receptor ; Combination Therapies; Cytokine-release Syndrome; B-cell; Antitumor-activity; Inhibitor Ibrutinib; Checkpoint Blockade; Pd-1 Blockade; Tumor Burden; Immunotherapy; Cd8(+); Improves
ISSN (print) / ISBN
2227-9059
e-ISSN
2227-9059
Journal
Biomedicines
Quellenangaben
Volume: 10,
Issue: 2,
Article Number: 307
Publisher
MDPI
Publishing Place
Basel, Switzerland
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Unit for Clinical Pharmacology (KKG-EKLiP)
Grants
SFB-TRR 338/1 2021452881907
Hector foundation
International Doctoral Program i-Target: Immunotargeting of Cancer - Elite Network of Bavaria
Melanoma Research Alliance Grants
Else Kroener-Fresenius-Stiftung
German Cancer Aid
Ernst-Jung-Stiftung
LMU Munichs Institutional Strategy LMUexcellent within German Excellence Initiative
Bundesministerium fuer Bildung und Forschung
European Research Council
German Research Foundation (DFG)
Fritz-Bender Foundation
Jose-Carreras Foundation
Marie Sklodowska-Curie Program Training Network for Optimizing Adoptive T Cell Therapy of Cancer - H2020 Program of the European Union
Hector foundation
International Doctoral Program i-Target: Immunotargeting of Cancer - Elite Network of Bavaria
Melanoma Research Alliance Grants
Else Kroener-Fresenius-Stiftung
German Cancer Aid
Ernst-Jung-Stiftung
LMU Munichs Institutional Strategy LMUexcellent within German Excellence Initiative
Bundesministerium fuer Bildung und Forschung
European Research Council
German Research Foundation (DFG)
Fritz-Bender Foundation
Jose-Carreras Foundation
Marie Sklodowska-Curie Program Training Network for Optimizing Adoptive T Cell Therapy of Cancer - H2020 Program of the European Union