Those antibodies with a high internalization rate were directly conjugated with a cytotoxic agent (auristatin MMAE) and tested in an in vitro ADC assay. 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. Briefly, plasmablasts were collected from patients and paired heavy and light chain antibody sequences were then obtained from individual cells. We analyzed blood plasmablasts from patients with non-progressing metastatic cancer using IRC™ technology. Here we show that Atreca’s Immune Repertoire Capture (IRC™) technology can identify potent anti-tumor antibodies with internalization activity applicable for ADC therapeutics from patients undergoing immunotherapy. 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. (ADCC/CDC) P1 The identification of potent anti-tumor antibodies for ADC therapeutics from patients undergoing immunotherapy Alexander Scholz, PhD 1, Jerald Aurellano 1, Michael Harbell, MS PhD 1, Danhui Zhang, MD PhD 1, Samantha O'Connor 1, May Sumi, BS 1, Beatriz Millare, BS 1, Felix Chu, MS 1, Sheila Fernandez 1, Cathrin Czupalla 1, Iraz Aydin, PhD 1, Amy Manning-Bog, PhD 1, Yvonne Leung, BS, PhD 1, Kevin Williamson, BS PhD 1, Chantia Carroll 1, Dongkyoon Kim, BS PhD 1, Xiaomu Chen, MS PhD 1, Sean Carroll, BS, PhD 1, Ish Dhawan, PhD 1, Ngan Nguyen, BS PhD 1, Shweta Thyagarajan 1, Mark Whidden 1, Gregg Espiritu Santo, BS PhD 1, Nicole Haaser, MS 1, Hibah Mahmood 1, Guy Cavet, PhD 1, Lawrence Steinman, MD 2, Tito Serafini, PhD 1, Wayne Volkmuth, BS PhD 1, Jonathan Benjamin, MD, PhD 1, William Robinson, MD 2, Norman Greenberg, PhD 1, Daniel Emerling, PhD 1, Jell DeFalco 1 1Atreca Inc, Redwood City, CA, USA 2Stanford University School of Medicine, Stanford, CA, USA Correspondence: Daniel Emerling 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.
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