Adapter CAR T Cells: From the Idea to the Clinic
A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".
Deadline for manuscript submissions: 31 December 2024 | Viewed by 1416
Special Issue Editor
Interests: (radio)immunotherapy and imaging of tumors; bispecific antibodies; genetically modified immune effector cells; autoimmunity
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Special Issue Information
Dear Colleagues,
At the end of the 1980s, researchers considered equipping T cells with synthetic receptors, thereby enabling them to recognize tumor cells in a T-cell-atypical, MHC-independent, and antibody-based manner. Later, these receptors were termed chimeric antigen receptors (CARs). A clinical breakthrough in CAR T cells occurred in 2017 when the FDA approved the first anti-CD19-directed CAR therapy. In the following years, besides the impressive efficacy of CAR T cells, major side effects became evident such as cytokine release syndrome and OFF-target tissue effects. After adoptive transfer into the patient, the regulation of the function of such conventional CAR T cells is quite limited. To overcome this limitation, adaptor CAR technologies were developed. In contrast to conventional CARs, the target specificity of adaptor CAR T cells is not provided by the extracellular domain of the CAR but is instead realized by a bispecific adaptor molecule, also known as a target module (TM). On one hand, the TM recognizes the target cell; on the other hand, it is capable of binding to the extracellular CAR domain. Adaptor CAR T cells are, therefore, highly flexible as the target specificity can easily be changed by replacing the adaptor molecule. Most importantly, adaptor CAR T cells are only active in the presence of the TM, as it is required for cross-linkage between the immune cell and the target cell. In a clinical setting, this concept allows simple regulation of the adaptor CAR T cells via a stop-and-go infusion strategy of the respective TM. The resulting improved safety of adaptor CAR technology may also facilitate the application of CAR technology to the treatment of other diseases, e.g., autoimmune diseases.
In this Special Issue, we focus on the development of adaptor CAR technology; its idea; its components; comparisons related to, e.g., bispecific antibody technologies; its application for gated targeting strategies; and the potential application of TMs as radioimmunotheranostics to improve the treatment of solid tumors and overcome the immune-suppressive tumor microenvironment.
Prof. Dr. Michael P. Bachmann
Guest Editor
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Keywords
- CAR T cell therapy
- chimeric antigen receptor
- bispecific antibody
- target module
- autoimmune diseases
- solid tumors
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