Novel C5a agonist-based dendritic cell vaccine in a murine model of melanoma.
A novel method to improve targeting and presentation of poorly immunogenic tumor-related antigens was investigated. This was performed with a molecular adjuvant constructed by covalently linking a response selective peptide agonist of C5a (YSFKDMP(MeL)aR) to known melanoma tumor-related antigens. C57Bl/6J mice were injected subcutaneously with bone marrow derived dendritic cells (DCs) pulsed with a melanoma epitope (TRP2-P2/Agonist), melanoma epitope tyrosinase (TYR/Agonist), a nonfunctional reverse conformation C5a agonist bound to TYR(reverse peptide) or DMSO-PBS vehicle. Mice were injected with the pulsed DCs and cytokines IL-2 and GMCSF three times prior to subcutaneous challenge with B16-F10 melanoma cells. All groups subsequently received DC vaccine boosters twice per week. Tumor growth was reduced and survival enhanced in mice immunized with the combination of TRP2-P2/Agonist and TYR/Agonist compared to mice receiving reverse peptide or vehicle.
Floreani
Anthony A
AA
Department of Internal Medicine Pulmonary/Critical Care, University of Nebraska Medical Center, Omaha, Nebraska, USA. aflorean@unmc.edu
Gunselman
Sandra J
SJ
Heires
Arthur J
AJ
Hauke
Ralph J
RJ
Tarantolo
Stefano
S
Jackson
John D
JD
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use*; D015936:Complement C5a / Q000819:agonists* / Q000235:genetics / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation*; D004195:Disease Models, Animal; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006131:Growth Inhibitors; D007376:Interleukin-2; D015936:Complement C5a; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase