Adapter CAR T Cells: From the Idea to the Clinic

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

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.