Prof. Zelig Eshhar, an Israeli immunologist at the Weizmann Institute of Science, is a pioneer of the CAR-T cell approach and its application for cancer therapy.

Eshhar’s seminal studies, at the Weizmann Institute in the mid-Eighties, led to the development of the first chimeric antibody-based receptors (CARs). Specifically, he engineered novel immuno-receptors and showed that they could bestow the ability to detect and kill target cells. 

Eshhar then designed and constructed modular CAR versions, including a single-chain variable fragment and intracellular T cell activation motifs (ITAM). Importantly, this rendered the CARs independent of critical TCR complex cofactors, thus removing a critical obstacle and further improving the efficacy and paving the way for effective treatment. 

Eshhar and his team envisaged the potential of this approach for cancer treatment early on. Eshhar focused on demonstrating the anti-cancer reactivity of CAR-T cells in murine experimental models. His pre-clinical studies in tumor-bearing animals defined the optimal CAR specificities, and treatment conditions required for effective and safe cancer eradication.

Eshar showed that CARs can target regulatory T cell activities to relieve inflammatory disorders. Today, treatment protocols using CAR-T cells are listed high at the NIH registry of clinical trials. Moreover, CAR-T cells targeting acute lymphoblastic leukemia (ALL) have been approved by the FDA as the first gene transfer-based therapy.

“Our biggest satisfaction was that CAR-T therapy was approved by the FDA and now patients benefit by getting the treatment all over the world,” Prof. Eshhar remarked.