{"entity":{"id":"zelig-eshhar","kind":"person","name":"Zelig Eshhar","aka":[],"tldr":"The immunologist who, in 1989, first gave a T cell an antibody's aim. Every CAR-T product on the market descends from that experiment.","summary":"Zelig Eshhar's laboratory at the Weizmann Institute of Science built the first chimeric antigen receptor. In Gross, Waks and Eshhar's 1989 paper in the Proceedings of the National Academy of Sciences, the variable domains of an antibody against trinitrophenyl were spliced onto the constant domains of the T-cell receptor alpha and beta chains and expressed in a cytotoxic T-cell hybridoma. The transfected cells killed and made interleukin-2 in response to the hapten without needing the major histocompatibility complex to present it, across strain and species barriers, and responded to immobilised conjugates, bypassing antigen processing altogether. Eshhar called the construct a \"T-body\", and his group's 1993 single-chain variable fragment design is the format every modern CAR uses. Every approved CAR-T product, from tisagenlecleucel to the BCMA products in myeloma, descends from it, with costimulatory domains added later by Michel Sadelain, Carl June and Dario Campana.\n\nPriority is genuinely contested and this record says so. Kuwana and colleagues in Japan built an antibody-variable and T-cell-receptor-constant chimera in 1987, two years earlier, and showed antigen-triggered calcium signalling; what the 1989 Weizmann paper added was redirected killing and cytokine secretion independent of the major histocompatibility complex. Which counts as the first chimeric antigen receptor depends on whether you require function. Eshhar later published repeatedly with Steven Rosenberg's group at the National Cancer Institute, including the first-in-human CAR trial from that collaboration, in ovarian cancer, which was negative; he continued on dual-specificity CARs and on CAR dosing and safety, and his recent papers carry a Tel Aviv Sourasky Medical Center affiliation.","asOf":"2026-09-25","links":[{"label":"Weizmann Institute of Science","url":"https://www.weizmann.ac.il"},{"label":"PubMed author search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Eshhar%20Z%5BAuthor%5D%20chimeric"}],"tags":["clinician-scientist","immunology","cell-therapy"],"related":[],"cancers":["all-leukemia","dlbcl","multiple-myeloma"],"sections":["cell-therapy","immunotherapy"],"technologies":["car-t"],"targets":["cd19"],"drugs":[],"companies":[],"institutions":["weizmann","tel-aviv-university","tel-aviv-sourasky"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":["paper-gross-eshhar-chimeric-receptor-pnas-1989"],"journals":[],"dependsOn":[],"notes":[],"role":"Immunologist; professor emeritus, Weizmann Institute of Science, latterly Immunology Laboratory, Tel Aviv Sourasky Medical Center","institutionId":"weizmann","specialisms":["Cancer immunology","Chimeric antigen receptors","Adoptive cell therapy","T-cell engineering"],"profiles":[{"label":"Weizmann Institute of Science","url":"https://www.weizmann.ac.il"},{"label":"PubMed author search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Eshhar%20Z%5BAuthor%5D%20chimeric"}],"papers":[{"title":"Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity","journal":"Proceedings of the National Academy of Sciences","year":1989,"doi":"10.1073/pnas.86.24.10024","note":"Gross G, Waks T, Eshhar Z. The first chimeric antigen receptor."},{"title":"Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors","journal":"Proceedings of the National Academy of Sciences","year":1993,"doi":"10.1073/pnas.90.2.720","note":"Eshhar Z, Waks T, Gross G, Schindler DG. The single-chain design modern CARs use."},{"title":"Therapeutic potential of T cell chimeric antigen receptors (CARs) in cancer treatment: counteracting off-tumor toxicities for safe CAR T cell therapy","journal":"Annual Review of Pharmacology and Toxicology","year":2016,"doi":"10.1146/annurev-pharmtox-010814-124844"},{"title":"Treatment of multiple myeloma using chimeric antigen receptor T cells with dual specificity","journal":"Cancer Immunology Research","year":2020,"doi":"10.1158/2326-6066.cir-20-0118"}]},"route":"/people/zelig-eshhar/","neighbours":{"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"}],"section":[{"id":"cell-therapy","kind":"section","name":"Cell Therapy","route":"/fronts/cell-therapy/"},{"id":"immunotherapy","kind":"section","name":"Immunotherapy","route":"/fronts/immunotherapy/"}],"technology":[{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"}],"target":[{"id":"cd19","kind":"target","name":"CD19","route":"/targets/cd19/"}],"institution":[{"id":"tel-aviv-sourasky","kind":"institution","name":"Tel Aviv Sourasky Medical Center","route":"/institutions/tel-aviv-sourasky/"},{"id":"tel-aviv-university","kind":"institution","name":"Tel Aviv University","route":"/institutions/tel-aviv-university/"},{"id":"weizmann","kind":"institution","name":"Weizmann Institute of Science","route":"/institutions/weizmann/"}],"bottleneck":[{"id":"b-manufacturing-cell-therapy","kind":"bottleneck","name":"Manufacturing cost and time for living and radioactive medicines","route":"/bottlenecks/b-manufacturing-cell-therapy/"}],"paper":[{"id":"paper-gross-eshhar-chimeric-receptor-pnas-1989","kind":"paper","name":"Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity","route":"/key-papers/paper-gross-eshhar-chimeric-receptor-pnas-1989/"}]}}