Yoshiyuki Koyama1,2, Tomoko Ito3,4, Aya Hasegawa4, Masazumi Eriguchi3, Toshio Inaba4, Takahiro Ushigusa4,5, Kikuya Sugiura4. 1. Japan Anti-tuberculosis Association, Shin-Yamanote Hospital, 3-6-1 Suwa-cho, Higashimurayama, Tokyo, 189-0021, Japan. drkoyama@vivid.ocn.ne.jp. 2. Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku-oraikita, Izumisano, Osaka, 598-8531, Japan. drkoyama@vivid.ocn.ne.jp. 3. Japan Anti-tuberculosis Association, Shin-Yamanote Hospital, 3-6-1 Suwa-cho, Higashimurayama, Tokyo, 189-0021, Japan. 4. Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku-oraikita, Izumisano, Osaka, 598-8531, Japan. 5. Kannai Animal Clinic, 6-3 Yoshida-cho, Naka-ku, Yokohama, Kanagawa, 231-0023, Japan.
Abstract
OBJECTIVES: To examine the potential of exosomes derived from the tumor cells, which had been genetically modified to express a Mycobacterium tuberculosis antigen, as a cancer vaccine aimed at overcoming the weak immunogenicity of tumor antigens. RESULTS: We transfected B16 melanoma cells with a plasmid encoding the M. tuberculosis antigen, early secretory antigenic target-6 (ESAT-6). The secreted exosomes bearing both tumor-associated antigens and the pathogenic antigen (or their epitopes) were collected. When the exosomes were injected into foot pads of mice, they significantly (p < 0.05) evoked cellular immunity against both ESAT-6, and B16 tumor cells. Intra-tumoral injection of the exosomes significantly suppressed (p < 0.001) tumor growth in syngeneic B16 tumor-bearing mice, while the exosomes derived from the non-transfected B16 cells showed no effect on tumor growth, although both exosomes should have similar tumor antigens. CONCLUSIONS: Exosomes bearing both tumor antigens and the M. tuberculosis antigen (or their epitopes) have a high potential as a candidate for cancer vaccine to overcome the immune escape by tumor cells.
OBJECTIVES: To examine the potential of exosomes derived from the tumor cells, which had been genetically modified to express a Mycobacterium tuberculosis antigen, as a cancer vaccine aimed at overcoming the weak immunogenicity of tumor antigens. RESULTS: We transfected B16 melanoma cells with a plasmid encoding the M. tuberculosis antigen, early secretory antigenic target-6 (ESAT-6). The secreted exosomes bearing both tumor-associated antigens and the pathogenic antigen (or their epitopes) were collected. When the exosomes were injected into foot pads of mice, they significantly (p < 0.05) evoked cellular immunity against both ESAT-6, and B16 tumor cells. Intra-tumoral injection of the exosomes significantly suppressed (p < 0.001) tumor growth in syngeneic B16 tumor-bearing mice, while the exosomes derived from the non-transfected B16 cells showed no effect on tumor growth, although both exosomes should have similar tumor antigens. CONCLUSIONS: Exosomes bearing both tumor antigens and the M. tuberculosis antigen (or their epitopes) have a high potential as a candidate for cancer vaccine to overcome the immune escape by tumor cells.
Entities:
Keywords:
Cancer vaccine; Early secretory antigenic target-6 (ESAT-6); Exogenous danger signal; Exosomes; Mycobacterium tuberculosis antigen; Neoantigens; Neoepitopes