Screening platform for identification of potent and specific nanobodies for (i) directing CAR-T cells to cancer cells, (ii) drug conjugation, or (iii) tumor imaging or diagnosis.
Identification of antibodies capable of mediating CAR-T killing is challenging due to several reasons. First, the antibody has to have certain affinity to allow for sufficient binding time permitting the T cell to kill the target cells. Second, the scFv derived from the antibody must be conserve the affinity and specificity, followed by fusion with the rest of the CAR construct. Third, the antibody must bind to the appropriate location of the cell surface protein on the cancer cell to allow a certain distance between the T cell surface and the tumor cell surface to form effect immune synapse. There is a need for technologies allowing for efficient identification of potent, specific antibodies for CAR-T cell therapies.
Dr. Xiaxin Hua and his team have developed Sequential Tumor-related Antibody and antigen Retrieving (STAR) technology that allows to efficiently identify nanobodies fully capable of binding to tumor cell surface antigens and guide the CAR-T cells in vivo to the specific tumors. Nanobodies are tested for cross-reactivity with other tissues in vivo. The technology was successfully validated for generating nanobodies for targeting AML and neuroendrocrine tumors
, tested in switchable CAR system.