Thus, a key factor in choosing which programs to use will be the skill level and comfort of the user.
William robinson immune repertoire capture software#
These range from bespoke command line tools written in various programming languages that require facility in a Linux terminal to software with fully developed graphical interfaces and no requirement for programming skills of any kind. Philadelphia (PA): AACR Cancer Res 2019 79(13 Suppl):Abstract nr 1543.A breathtaking array of computational tools are available for repertoire analysis. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019 2019 Mar 29-Apr 3 Atlanta, GA. Discovery of antibodies for ADC therapy from cancer patients who show durable clinical response to checkpoint inhibitors. Greenberg, Daniel Emerling, Jeff DeFalco.
Serafini, Wayne Volkmuth, Jonathan Benjamin, William H. Carroll, Ish Dhawan, Ngan Nguyen, Shweta Thyagarajan, Mark Whidden, Gregg Espiritu Santo, Nicole Haaser, Guy Cavet, Lawrence Steinman, Tito A. Czupalla, Iraz Aydin, Amy Manning-Bog, Yvonne Leung, Kevin Williamson, Chantia Carroll, Dongkyoon Kim, Xiaomu Chen, Sean M. Overall, we show that the antibody repertoires of cancer patients contain tumor-selective antibodies with potent internalization properties and strong ADC therapeutic potential.Ĭitation Format: Alexander Scholz, Jerald Aurellano, Michael Harbell, Danhui Zhang, Samantha O'Connor, Beatriz Millare, Felix Chu, Sheila Fernandez, Cathrin J. Furthermore, we demonstrate that the internalizing antibodies were able to deliver a cytotoxic payload to induce tumor cell death. In this study, we used Atreca’s IRC™ platform to identify patient-derived antibodies that bind to tumor-selective antigens and a subset that also internalize into cancer cells.
When used in combination with a secondary antibody conjugated to the MMAE cytotoxic agent, internalizing antibodies were able to induce target cell death in vitro. Of these, several also showed internalization into human A549 lung tumor cells when measured through the detection of a pH-sensitive dye. We identified multiple patient-derived antibodies, from several cancer types, that bound to human tumor tissue, but not adjacent normal tissue. Those antibodies with a high internalization rate were subsequently tested for in vitro ADC activity using a secondary antibody conjugated with the auristatin MMAE. Antibodies representing expanded clonal families were expressed recombinantly and analyzed for binding to human tumor and non-tumor tissues, as well as for internalization activity using a pH-sensitive dye and cancer cell lines. To identify anti-tumor antibodies with hallmarks suitable for ADC applications, we used IRC™ to analyze blood plasmablasts, a type of antibody secreting activated B cell collected from patients with non‐progressing metastatic cancer. Here we demonstrate, using Atreca’s Immune Repertoire Capture (IRC™) technology, that we can identify tumor selective antibodies that have internalization activity suitable for ADC therapeutics directly from cancer patients showing durable clinical response to checkpoint inhibitors. Only a select number of tumor-selective internalizing antibodies have been identified, and this has limited the scope of ADC therapeutic strategies in the clinic. Successful anti-tumor therapy using antibody-drug conjugates (ADCs) depends, in part, on antibodies that bind tumor selective targets that are subsequently internalized at a high rate into tumor cells.
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