A novel approach to cancer immunotherapy: tumor cells decorated with CD80 generate effective antitumor immunity.
Malignant cells often elude the immune system by lacking costimulatory signals required for the generation of effective antitumor immunity. Immunization with tumor cells genetically modified to express costimulatory molecules is a highly promising approach to cancer immunotherapy. However, genetic modification of tumor cells is not only labor/time intensive but is also less efficient and bears safety concerns. To override these complications, we have recently developed a novel technology that allows for efficient and durable display of exogenous proteins on the surface of a cell within 2 h. This technology involves modification of the cell membrane with a biotin derivative and decoration of biotinylated cells with proteins chimeric with core streptavidin. A chimeric molecule composed of the extracellular domains of the human CD80 costimulatory molecule and core streptavidin (CD80-SA) was efficiently displayed on the cell surface, where it persisted with a t(1/2) of >10 days in vivo. Tumors from patients with advanced stage gynecologic cancers decorated with CD80-SA elicited potent ex vivo tumor-specific proliferative and cytotoxic responses in autologous lymphocytes. Immunization with tumor cells decorated with CD80-SA completely prevented tumor growth in an aggressive model of mouse lymphoma. This technology may serve as a fast, efficient, and safe alternative to gene transfer approaches for engineering tumor cells for use in immunotherapy and research.
Singh
Narendra P
NP
Institute for Cellular Therapeutics, University of Louisville, Louisville, Kentucky 40202, USA.
Yolcu
Esma S
ES
Taylor
Douglas D
DD
Gercel-Taylor
Cicek
C
Metzinger
Daniel S
DS
Dreisbach
Stephen K
SK
Shirwan
Haval
H
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001710:Biotin / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D005260:Female; D018014:Gene Transfer Techniques; D005833:Genital Neoplasms, Female / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019809:Streptavidin / Q000031:analogs & derivatives* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured
D018122:B7-1 Antigen; D011993:Recombinant Fusion Proteins; D001710:Biotin; D019809:Streptavidin