Antitumor and anti-angiogenesis immunity induced by CR-SEREX-identified Xenopus RHAMM.
Immunization with xenogeneic antigens is an attractive approach to induce cross-reactive humoral and cellular immunity to inhibit tumor growth or angiogenesis. To identify novel xenogenic targets for immunotherapy, we have developed a modified serological expression cloning (SEREX) strategy, termed Cross-reactive SEREX (CR-SEREX). Among 78 positive clones identified by CR-SEREX, Xenopus receptor for hyaluronic-acid-mediated motility (xRHAMM) was most frequently identified (18 times), indicating the strongest immunogenic potential for xenogenic immunotherapy. A DNA vaccine based on xRHAMM effectively induced a protective antitumor immunity against local tumor and lung metastasis in B16 melanoma mouse models. Angiogenesis was inhibited and cell apoptosis was increased within tumors. Antitumor activity of xRHAMM worked through stimulation of an antigen-specific cellular response as well as through a specific humoral response against RHAMM, as confirmed by the depletion of immune cell subsets in vivo. Thus, a xenogenic vaccine based on xRHAMM induced an effective immunity against B16 melanoma cells and endothelial cells.
Yang
Han Shuo
HS
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. yhansh@scu.edu.cn
Zhang
Dong Mei
DM
Deng
Hong Xin
HX
Peng
Feng
F
Wei
Yu Quan
YQ
D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D003001:Cloning, Molecular; D003429:Cross Reactions / Q000276:immunology; D018960:Hyaluronan Receptors / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D008546:Melanoma, Experimental / Q000098:blood supply / Q000276:immunology / Q000628:therapy*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000276:immunology*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D014982:Xenopus laevis / Q000235:genetics / Q000276:immunology
D015478:Antigens, Heterophile; D019496:Cancer Vaccines; D018960:Hyaluronan Receptors; D019444:Vaccines, DNA