Monoclonal TCR-mediated tumor cell killing

Liddy, N. et al. Nature medicine. 2012 Jun;18(6):980-7.

Speaker: Jia-Ying Hung (洪家瑩)                                 Time: 15:00~16:00, Nov. 14, 2012

Commentator: Dr. Bei-chang Yang (楊倍昌 老師)     Place: Room 601

Abstract:

T cell receptor (TCR) is involved T cell-mediated eradication of cancer cells. TCR binds to antigen with a restricted format and specifically recognizes processed peptides bound to major histocompatibility complex (pMHC) presented on cell surface. However, specific TCR–mediated antigen recognition and activation is malfunction in majority of patient with cancer. To enhance the T cell function in malignant cancer cells killing, the authors developed four immune-mobilizing monoclonal TCRs (ImmTACs): (1) ImmTAC-NYE, (2) ImmTAC-gp100, (3) ImmTAC-MAGE, and (4)ImmTAC-MEL. These ImmTACs are derived from four different tumor-associated antigens: (1) gp100, amelanocyte differentiation antigen; (2) MAGE-A3, a cancer testis antigen expressed by a wide variety of tumors; (3) Melan-A/MART-1, a lineage-specific antigen presented in melanoma; (4) NY-ESO-1, a cancer testis antigen presented in multiple myeloma and melanoma and some other cancers. Each ImmTAC is composed of a high affinity tumor-associated epitope-specific monoclonal TCR and a humanized cluster of differentiation 3 (CD3) specific single chain antibody fragment (scFv), which is fused to monoclonal TCR. They found that these ImmTACs are able to effectively recruit T cells towards malignant cancer cells and promote tumor antigen recognition despite of low surface epitope densities. In addition, they also showed that ImmTACs can trigger maglignantcancer killing by T cells and cause tumor regression in vivo. Taken together, the authors demonstrated that ImmTACs can potently overcome the immune tolerance of cancer cells and potentially used as a new approach for cancer immunotherapy.

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