title: Eradication of melanomas by targeted elimination of a minor subset of tumor cells.
abstract: Proceeding on the assumption that all cancer cells have equal malignant capacities, current regimens in cancer therapy attempt to eradicate all malignant cells of a tumor lesion. Using in vivo targeting of tumor cell subsets, we demonstrate that selective elimination of a definite, minor tumor cell subpopulation is particularly effective in eradicating established melanoma lesions irrespective of the bulk of cancer cells. Tumor cell subsets were specifically eliminated in a tumor lesion by adoptive transfer of engineered cytotoxic T cells redirected in an antigen-restricted manner via a chimeric antigen receptor. Targeted elimination of less than 2% of the tumor cells that coexpress high molecular weight melanoma-associated antigen (HMW-MAA) (melanoma-associated chondroitin sulfate proteoglycan, MCSP) and CD20 lastingly eradicated melanoma lesions, whereas targeting of any random 10% tumor cell subset was not effective. Our data challenge the biological therapy and current drug development paradigms in the treatment of cancer.
authors.affiliation: Department I of Internal Medicine, and Center for Molecular Medicine Cologne, University of Cologne, D-50931 Cologne, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schmidt
authors.forename: Caroline
authors.initials: C
authors.lastname: Kopecky
authors.forename: Andreas
authors.initials: A
authors.lastname: Hombach
authors.forename: Paola
authors.initials: P
authors.lastname: Zigrino
authors.forename: Cornelia
authors.initials: C
authors.lastname: Mauch
authors.forename: Hinrich
authors.initials: H
authors.lastname: Abken
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018951:Antigens, CD20 / Q000276:immunology*; D002461:Cell Line, Transformed; D006801:Humans; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D058950:Melanoma-Specific Antigens / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D009363:Neoplasm Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D018951:Antigens, CD20; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins