![]() Dose limiting toxicity relates to systemic IL2 toxicity. application has been shown already in several clinical trials in melanoma and neuroblastoma. Clinical efficacy of the immunocytokine by i.v. The humanized antibody portion targets the GD2 ganglioside antigen expressed on a variety of tumors of neuroectodermal origin. The study was approved by Sutter Health Institutional Review Board, approval #2016.148-1 P2 Intratumoral application of hu14.18-IL2 for treatment of GD2+ pediatric malignancies: A novel immunotherapeutic approach aiming at in-situ vaccination Romana Gugenberger, PhD 1, Zachary Morris, MD, PhD 2, Oliver Mutschlechner 1, Paul Sondel, MD, PhD 2, Hans Loibner, PhD 1 1Apeiron Biologics AG, Vienna, Austria 2University of Wisconsin, Madison, WI, USA Correspondence: Hans Loibner is an antibody-cytokine fusion protein that combines targeting and immune activation of a human IgG1 monoclonal antibody with the immune stimulatory function of IL2. Furthermore, we demonstrate that these antibodies can deliver a cytotoxic payload to target tumor cells to induce cell death. In this study we demonstrate that patient-derived antibodies which bind to public tumor-selective antigens and internalize into cancer cells can be identified by our IRC™ technology. These internalizing antibodies were able to induce target cell death in vitro when conjugated directly or indirectly to a cytotoxic agent across several human tumor cell lines. Patient-derived antibodies from several cancer types bound to human tumor tissue but not adjacent normal tissue and also internalized into A549 lung tumor cells. 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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