Antitumor effects of systemic and local immunization with a CTL-directed peptide in combination with a local injection of OK-432.
OBJECTIVE
The accumulation of T cells into the tumor site is crucial for the elicitation of in vivo antitumor effects after cancer vaccination. In this study, we investigated the antitumor effects and associated mechanisms of action that were induced by systemic and local immunization with a CTL-directed peptide in combination with a peritumoral injection of a streptococcal preparation, OK-432.


RESULTS
The human SART3(315-323) peptide, which has the potential to induce human leukocyte antigen-A24-restricted CTLs, not only has the same amino acid sequence as the mouse SART3, but also has the capacity for binding to H-2K(d) molecules. Therefore, the SART3(315-323) peptide could be used as a tumor antigen-derived peptide in H-2(d) mice. Systemic immunization with the SART3(315-323) peptide and the subsequent peritumoral injection of both the SART3(315-323) peptide and OK-432 effectively induced peptide-specific and colon26 carcinoma-reactive CTLs in BALB/c mice. The combination therapy suppressed the growth of s.c. established colon26 carcinoma. The accumulation of both CD8(+) and CD4(+) T cells into the tumor site was more apparent in mice treated with the combination therapy than in those treated with other protocols. In addition, the level of IgG reactive to the administered SART3(315-323) peptide increased in mice that were treated with the combination therapy.


CONCLUSIONS
These results indicate that antitumor effects could be efficiently induced by a combination therapy that included systemic and local immunization with a CTL-directed peptide together with a local injection of OK-432.
Cancer Vaccine Development Division, Kurume University Research Center for Innovative Cancer Therapy, Kurume, Japan.
Takeharu
T
Ono
Mamoru
M
Harada
Akira
A
Yamada
Masahiro
M
Tanaka
Yukari
Y
Takao
Yasuaki
Y
Tanaka
Takashi
T
Mine
Kikuo
K
Sakamoto
Tadashi
T
Nakashima
Kyogo
K
Itoh
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D010844:Picibanil / Q000008:administration & dosage / Q000627:therapeutic use*; D016601:RNA-Binding Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D007074:Immunoglobulin G; D010446:Peptide Fragments; D016601:RNA-Binding Proteins; C416530:SART3 protein, human; D010844:Picibanil