Nature Biotechnology 24, 205 - 209 (2006)
Published online: 29 January 2006; | doi:10.1038/nbt1185
Identification and immunotherapeutic targeting of antigens induced by chemotherapyBonnee Rubinfeld, Archana Upadhyay, Suzanna L Clark, Sharon E Fong, Victoria Smith, Hartmut Koeppen, Sarajane Ross
& Paul Polakis
Departments of Molecular Oncology, Pathology and Translational Oncology, Genentech, Inc., 1 DNA Way, S. San Francisco, California 94080, USA.
Correspondence should be addressed to Paul Polakis ppolakis@gene.com Cancer cells differ from normal cells in their response to chemotherapy. We exploited this dissimilarity by identifying and targeting tumor-specific, cell-surface proteins whose expression is induced by the chemotherapeutic irinotecan (CPT-11; Camptosar). A cytotoxin-armed antibody reactive with one of these drug-induced surface proteins, the LY6D/E48 antigen, originally identified as the target of a monoclonal antibody reactive with squamous cell carcinomas, caused complete regression of colorectal tumor xenografts in mice treated with CPT-11, whereas either agent alone was less effective. These results suggest that a positive therapeutic index may be generated for other drug combinations by immunotherapeutic targeting of chemotherapy-induced antigens.
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