title: Administration of sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate conjugated GP100(25-33) peptide-coupled spleen cells effectively mounts antigen-specific immune response against mouse melanoma.
abstract: It remains a top research priority to develop immunotherapeutic approaches to induce potent antigen-specific immune responses against tumors. However, in spite of some promising results, most strategies are ineffective because they generate low numbers of tumor-reactive cytotoxic T lymphocytes (CTLs). Here we designed a strategy to enhance antigen-specific immune response via administering sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate (sulfo-SMCC)-conjugated melanoma tumor antigen GP10025-33 peptide-coupled syngeneic spleen cells in a mouse model of melanoma. We found that infusion of GP10025-33 peptide-coupled spleen cells significantly attenuated the growth of melanoma in prophylactic and therapeutic immunizations. Consistent with these findings, the adoptive transfer of spleen cells from immunized mice to naïve syngeneic mice was able to transfer anti-tumor effect, suggesting that GP10025-33 peptide-specific immune response was induced. Further studies showed that, CD8+ T cell proliferation and the frequency of interferon (IFN)-γ-producing CD8+ T cells upon ex vivo stimulation by GP10025-33 were significantly increased compared to control groups. Tumor antigen, GP10025-23 specific immune response was also confirmed by ELISpot and GP100-tetramer assays. This approach is simple, easy-handled, and efficiently delivering antigens to lymphoid tissues. Our study offers an opportunity for clinically translating this approach into tumor immunotherapy.
authors.affiliation: Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Chang
authors.affiliation: Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing, China; Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL32610, USA. Electronic address: cqx65@yahoo.com.
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Xia
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D018796:Immunoconjugates / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology; D008301:Maleimides / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D008545:Melanoma / Q000276:immunology* / Q000517:prevention & control* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D013154:Spleen / Q000166:cytology* / Q000276:immunology; D058951:gp100 Melanoma Antigen / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D018796:Immunoconjugates; D008301:Maleimides; D010455:Peptides; D058951:gp100 Melanoma Antigen; C071675:sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate; D007371:Interferon-gamma
keywords: Immunotherapy; Melanoma; Peptide coupling; SMCC; Splenocytes