Antitumor activity of an anti‐CD98 antibody |
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| Authors: | Joseph M. Cantor Hoang Tran Dana Duey John Lippincott Joseph Zachwieja Mark H. Ginsberg Edward H. van der Horst |
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| Affiliation: | 1. School of Medicine, University of California—San Diego, La Jolla, CA;2. Pre‐Clinical Development, Igenica Biotherapeutics, CA |
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| Abstract: | CD98 is expressed on several tissue types and specifically upregulated on fast‐cycling cells undergoing clonal expansion. Various solid (e.g., nonsmall cell lung carcinoma) as well as hematological malignancies (e.g., acute myeloid leukemia) overexpress CD98. We have identified a CD98‐specific mouse monoclonal antibody that exhibits potent preclinical antitumor activity against established lymphoma tumor xenografts. Additionally, the humanized antibody designated IGN523 demonstrated robust tumor growth inhibition in leukemic cell‐line derived xenograft models and was as efficacious as standard of care carboplatin in patient‐derived nonsmall lung cancer xenografts. In vitro studies revealed that IGN523 elicited strong ADCC activity, induced lysosomal membrane permeabilization and inhibited essential amino acid transport function, ultimately resulting in caspase‐3 and ‐7‐mediated apoptosis of tumor cells. IGN523 is currently being evaluated in a Phase I clinical trial for acute myeloid leukemia (NCT02040506). Furthermore, preclinical data support the therapeutic potential of IGN523 in solid tumors. |
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| Keywords: | phenotypic screening anti‐CD98 monoclonal antibody multiple mechanism of action acute myeloid leukemia non‐small cell lung cancer |
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