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33rd Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2018)

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Anti-tumor therapy with antibody-drug conjugates ADCs is predicated on the identification of antibodies that demonstrate suitable selectivity for tumor cells that are also internalized upon binding their cognate target. Remarkably, only a select number of such antibodies with the propensity to internalize have been identified, limiting the range and breadth of ADC therapeutics in the clinic. Briefly, plasmablasts were collected from patients and paired heavy and light chain antibody sequences were then obtained from individual cells. Antibody sequences representing expanded clonal families were subsequently expressed and analyzed for their ability to i bind to human tumor and non-tumor tissues and ii internalize into cancer cells when labeled with a pH-sensitive dye. Those antibodies with a high internalization rate were directly conjugated with a cytotoxic agent auristatin MMAE and tested in an in vitro ADC assay.
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