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Antitumor Effects of Systemic and Local Immunization with a CTL-Directed Peptide in Combination with a Local Injection of OK-432

Authors' Affiliations: ¹ Cancer Vaccine Development Division, Kurume University Research Center for Innovative Cancer Therapy, Departments of ² Immunology and ³ Otorhinolaryngology and Head and Neck Surgery, Kurume University School of Medicine, ⁴ Center of the 21st Century COE Program for Medical Science, Kurume University, Kurume, Japan

Requests for reprints: Mamoru Harada, Department of Immunology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan. Phone: 81-942-31-7744; Fax: 81-942-31-7745; E-mail: haramamo{at}med.kurume-u.ac.jp.

Purpose: 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.

Experimental Design and 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.

Conclusion: 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.

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