Monoclonal antibodies targeted against melanoma and ovarian tumors enhance dendritic cell-mediated cross-presentation of tumor-associated antigens and efficiently cross-prime CD8+ T cells.
Dendritic cells (DCs) constitute very attractive vectors for cancer immunotherapy due to their ability to efficiently capture and present tumor antigens, which initiates tumor-directed T-cell responses. Because the initiation of cytotoxic anti-tumor immune responses requires the cross-presentation mechanism, antigen targeting to DCs represents a very important step in the chain of events that constitutes the cross-priming immune process. In the current study, we explored the ability of DCs loaded with antibody-coated melanoma and ovarian carcinoma tumor cells to cross-present tumor antigens to CD8+ T cells and elicit in vitro anti-tumor immune responses. Coating melanoma and ovarian cancer cells with monoclonal antibodies against different surface antigens (CD44, ME491, LFA-3, and CD24) expressed by the tumor cells promoted the cross-presentation of the tumor-associated antigens as MART-1, gp100, tyrosinase, and NY-ESO-1 by DCs to CD8+ T. These tumor antigen-specific CD8+ T-cell populations resulting from the DC-mediated cross-priming process were identified using specific immune tetramers and were a few fold larger than the ones generated using peptide-pulsed or apoptotic tumor cell-loaded DCs. The CD8+ T cells generated by DCs loaded with monoclonal antibody-coated tumor cells were cytotoxic against the primary melanoma and ovarian carcinoma cells. Thus, targeting monoclonal antibody-coated tumor cells to DCs is a novel method that opens new perspectives for immunotherapy strategies.
Cioca
Daniel Petru
DP
Immunology Department, Timisoara Medical University, Timisoara, Romania. dcioca@personal.ro
Deak
Erika
E
Cioca
Flavius
F
Paunescu
Virgil
V
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology*; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000276:immunology*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm