A Novel Bispecific Antibody and a Method for One-step Differentiating, Expanding, and Arming T Cells
Adoptive T cell transfer, which involves the ex vivo expansion of the cancer patient’s T cells and intravenous injection back to the patient, can effectively mediate tumor regression. However, lack of tumor specificity of most expanded T cells and time-consuming of generating tumor-specific T cells severely restrict in vivo survival time and the anti-cancer ability of these ex vivo expanded T cells. Here, we developed kinds of bispecific antibodies (BsAbs) by fusing an anti-CD3 antibody with anti-tumor antibody to form α-tumor/α-CD3 BsAbs. Addition of these BsAbs into culture medium of human peripheral blood mononuclear cells (PBMCs) can efficiently differentiate, expand, and arm human CD8 CD3 T cell to selectively eliminate cancer cells. This culture process does not need the addition of mouse anti-CD3 antibody OKT3, which has been widely used in ex vivo expansion of human CD3 T cell for clinical T cell therapy, including CAR-T cells. The BsAb culture method can efficiently stimulate the differentiation of human CD3 T cell (>90%) from human PBMCs and can maintain T cell proliferation, which is comparable to traditional OKT3 culture method. During the BsAb culture process, BsAb can effectively arm to the surface of CD3 T cells, transforming naïve T cells into cancer specific T cells. Contact of BsAb-armed T cells with cancer cells significantly increases the release of T cell’s cytotoxic factors, including: perforin, granzyme, INF-γ and TNF-α, thus, enhances the cancer killing efficacy of T cells. This strategy provides a simple method for differentiating, expanding, and arming human CD3 T cell by one-step addition of BsAb into human PBMC culture medium, allowing enhanced specific targeting and therapeutic efficacy of human T cells for tumors in the clinic.
PCT applications submitted in 2018.
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