Journal
VACCINES
Volume 10, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/vaccines10111845
Keywords
adoptive cell therapy; CAR T cells; infiltration; cellular engineering; immunotherapy
Categories
Funding
- Marie Sklodowska-Curie Program Training Network for Optimizing Adoptive T Cell Therapy of Cancer - H2020 Program of the European Union [409510]
- Hector Foundation
- International Doctoral Program i-Target: Immunotargeting of Cancer - Elite Network of Bavaria
- Melanoma Research Alliance [756017]
- Else Kroner-Fresenius-Stiftung
- Wilhelm-Sander-Foundation
- German Cancer Aid
- Ernst-Jung-Stiftung
- LMU Munich's Institutional Strategy LMUexcellent
- Bavarian Ministry of Economical Affairs
- Deutsche Jose-Carreras Leukaemie Stiftung
- Go-Bio initiative
- Bundesministerium fur Bildung und Forschung
- European Research Council [SFB-TRR 338/1 2021-452881907]
- German Research Foundation (DFG)
- Fritz-Bender Foundation
- Wilhelm-Sander-Stiftung
- [955575]
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Adoptive cell therapy and chimeric antigen receptor T cell therapy are potential strategies for cancer treatment, but their effectiveness in solid tumors is limited. One of the main challenges is the poor access of transferred T cells to the tumor site. Engineering T cells is being explored to improve the efficacy of adoptive cell therapy in solid tumors.
Adoptive cell therapy (ACT) and chimeric antigen receptor (CAR) T cell therapy in particular represents an adaptive, yet versatile strategy for cancer treatment. Convincing results in the treatment of hematological malignancies have led to FDA approval for several CAR T cell therapies in defined refractory diseases. In contrast, the treatment of solid tumors with adoptively transferred T cells has not demonstrated convincing efficacy in clinical trials. One of the main reasons for ACT failure in solid tumors is poor trafficking or access of transferred T cells to the tumor site. Tumors employ a variety of mechanisms shielding themselves from immune cell infiltrates, often translating to only fractions of transferred T cells reaching the tumor site. To overcome this bottleneck, extensive efforts are being undertaken at engineering T cells to improve ACT access to solid tumors. In this review, we provide an overview of the immune cell infiltrate in human tumors and the mechanisms tumors employ toward immune exclusion. We will discuss ways in which T cells can be engineered to circumvent these barriers. We give an outlook on ongoing clinical trials targeting immune cell migration to improve ACT and its perspective in solid tumors.
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