Dendritic cell based personalized immunotherapy based on cancer antigen research.
Human tumor antigens were identified using various immunological and genetic methods, and immune responses to the identified antigens were evaluated in cancer patients. Autologous tumor specific unique antigens derived from genetic alterations in cancer cells were isolated from patients with favorable prognosis after immunotherapy, indicating that they are attractive targets for immunotherapy. Immunogenicity of shared antigens was found to differ among patients due to antigen expression in cancer cells and patients' immunoreactivity. These observations suggest that personalization may be applied for cancer immunotherapy. We therefore developed intratumoral DC administration protocols that are able to induce immune responses to both unique and shared tumor antigens expressed in each individual cancer. By combining cryoablative tumor pretreatment and TLR stimulated DC, the anti-tumor effect of the intratumoral DC administration was significantly augmented in a murine tumor model. This improved protocol enhanced systemic induction of anti-tumor CD8+ CTL, and was able to regress relatively large remote untreated tumors. In clinical trials, systemic immune induction was observed by intratumoral DC administration following cryoablative tumor treatment, although anti-tumor effects are relatively weak, indicating that additional interventions are required for more effective immunotherapy.
Kawakami
Yutaka
Y
Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University, School of Medicine, Tokyo, Japan. yutakawa@sc.itc.keio.ac.jp
Fujita
Tomonobu
T
Kudo
Chie
C
Sakurai
Toshiharu
T
Udagawa
Masaru
M
Yaguchi
Tomonori
T
Hasegawa
Go
G
Hayashi
Emiko
E
Ueda
Yoko
Y
Iwata
Tomoko
T
Wang
Qinfu
Q
Okada
Starlyn
S
Tsukamoto
Nobuo
N
Matsuzaki
Yuriko
Y
Sumimoto
Hidetoshi
H
D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D019496:Cancer Vaccines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D006801:Humans; D007107:Immune System / Q000378:metabolism; D007167:Immunotherapy / Q000379:methods*; D016219:Immunotherapy, Adoptive / Q000379:methods; D051379:Mice; D008957:Models, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines