Antitumor activity of an anti-CD98 antibody

  • Int J Cancer. 2015 Aug 1;137(3):710-20. doi: 10.1002/ijc.29415.
Gregory M Hayes  1 ,  Lawrence Chinn  1 ,  Joseph M Cantor  2 ,  Belinda Cairns  1 ,  Zoia Levashova  1 ,  Hoang Tran  1 ,  Timothy Velilla  1 ,  Dana Duey  1 ,  John Lippincott  1 ,  Joseph Zachwieja  1 ,  Mark H Ginsberg  2 ,  Edward H van der Horst  1
Affiliations
  • 1. Pre-Clinical Development, Igenica Biotherapeutics, CA.
  • 2. School of Medicine, University of California-San Diego, La Jolla, CA.
PMID: 25556716 DOI: 10.1002/ijc.29415
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.

Keywords
acute myeloid leukemia; anti-CD98 monoclonal antibody; multiple mechanism of action; non-small cell lung cancer; phenotypic screening.
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