Harrer, Dennis Christoph and Li, Sin-Syue and Kaljanac, Marcell and Barden, Markus and Pan, Hong and Abken, Hinrich (2023) Fine-tuning the antigen sensitivity of CAR T cells: emerging strategies and current challenges. FRONTIERS IN IMMUNOLOGY, 14: 1321596. ISSN 1664-3224,
Full text not available from this repository. (Request a copy)Abstract
Chimeric antigen receptor (CAR) T cells are "living drugs" that specifically recognize their target antigen through an antibody-derived binding domain resulting in T cell activation, expansion, and destruction of cognate target cells. The FDA/EMA approval of CAR T cells for the treatment of B cell malignancies established CAR T cell therapy as an emerging pillar of modern immunotherapy. However, nearly every second patient undergoing CAR T cell therapy is suffering from disease relapse within the first two years which is thought to be due to downregulation or loss of the CAR target antigen on cancer cells, along with decreased functional capacities known as T cell exhaustion. Antigen downregulation below CAR activation threshold leaves the T cell silent, rendering CAR T cell therapy ineffective. With the application of CAR T cells for the treatment of a growing number of malignant diseases, particularly solid tumors, there is a need for augmenting CAR sensitivity to target antigen present at low densities on cancer cells. Here, we discuss upcoming strategies and current challenges in designing CARs for recognition of antigen low cancer cells, aiming at augmenting sensitivity and finally therapeutic efficacy while reducing the risk of tumor relapse.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | IMMUNE ESCAPE; B-ALL; AFFINITY; NEUROBLASTOMA; RESISTANCE; TUMORS; CAR; antigen downregulation; antigen escape; antigen sensitivity; targeting selectivity |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Mar 2024 11:06 |
| Last Modified: | 13 Mar 2024 06:28 |
| URI: | https://pred.uni-regensburg.de/id/eprint/59432 |
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