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Identification and immunotherapeutic targeting of antigens induced by chemotherapy

Nature Biotechnology volume 24, pages 205–209 (2006)Cite this article

Abstract

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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Figure 1: mRNA transcripts coding for cell-surface proteins induced by CPT-11.
Figure 2: Expression of mouse intestinal transcripts homologous to those induced in human tumor xenografts.
Figure 3: Induction of cell-surface reactive LY6D/E48 protein in vitro by CPT-11 and SN-38.
Figure 4: Anti-tumor activity of CPT-11 combined with anti-LY6D/E48-drug conjugate.

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Acknowledgements

We thank Peter Senter and Damon Meyer for preparation of drug-conjugated antibodies, Tracey McKenna, Angela Lamb, JoAnne Hongo and Kurt Schroeder for generation and purification of monoclonal antibodies to LY6D/E48 and technical assistance.

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Authors and Affiliations

  1. Departments of Molecular Oncology, Pathology and Translational Oncology, Genentech, Inc., 1 DNA Way, S. San Francisco, 94080, California, USA

    Bonnee Rubinfeld, Archana Upadhyay, Suzanna L Clark, Sharon E Fong, Victoria Smith, Hartmut Koeppen, Sarajane Ross & Paul Polakis

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  1. Bonnee Rubinfeld
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Correspondence to Paul Polakis.

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Supplementary information

Supplementary Table 1

Transcripts induced in Colo205 tumor xenografts exposed to CPT-11. (PDF 51 kb)

Supplementary Table 2

Transcripts induced in the intestine of mice exposed to CPT-11. (PDF 46 kb)

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Rubinfeld, B., Upadhyay, A., Clark, S. et al. Identification and immunotherapeutic targeting of antigens induced by chemotherapy. Nat Biotechnol 24, 205–209 (2006). https://doi.org/10.1038/nbt1185

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