Identification and immunotherapeutic targeting of antigens induced by chemotherapy.
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.
Rubinfeld
Bonnee
B
Departments of Molecular Oncology, Pathology and Translational Oncology, Genentech, Inc., 1 DNA Way, S. San Francisco, California 94080, USA.
Upadhyay
Archana
A
Clark
Suzanna L
SL
Fong
Sharon E
SE
Smith
Victoria
V
Koeppen
Hartmut
H
Ross
Sarajane
S
Polakis
Paul
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001483:Base Sequence; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000276:immunology*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D000077146:Irinotecan; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D008565:Membrane Proteins; D000077146:Irinotecan; D002166:Camptothecin