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The ultimate goal of cancer research is the identification of a unique target on cancer cells that can be utilized for directed treatment, leaving normal cell populations unharmed. Due to the clonal heterogeneity in multiple myeloma (MM), this isn’t an easy task, as specific targets can change as the disease progresses and there are often differences between individual patients. Searching for such targets has been made easier by transcriptome or proteasome analyses, but these will often miss proteins with post-translational modifications or conformation-dependent active sites.
In a study carried out by Naoki Hosen, from Osaka University Graduate School of Medicine, Osaka, Japan, and a large team of researchers, cancer-specific monoclonal antibodies (mAbs) were identified, and they worked backward to identify the relevant antigens. Their findings were published in Nature Medicine in November 2017.
This pre-clinical study outlines highly promising data showing that the active conformation of integrin-β7 can be used as an immunotherapeutic target to generate MM-specific CAR T-cells. The researchers used a novel methodology to search for epitopes that could be missed by other screening methods, opening up the possibility of further as yet undiscovered epitopes that are cancer-specific only in their active state. The murine experiments with MMG49 CAR T-cells pave the way for further development of this CAR-T construct, such as fully humanizing the single chain variable fragment and entry of the CAR-T construct into clinical trials.
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