No abstract

Purpose:The accumulation of Tcells 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][316][317][318][319][320][321][322][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.

Hepatitis C virus (HCV) is a single‐strand RNA virus. Approximately 170 million people around the world are persistently infected and are at risk of liver cirrhosis or cancer. There is an urgent need to develop both therapeutic and diagnostic modalities of HCV. One approach to achieve these goals would be to determine highly immunodominant HCV peptides which are recognized by both cellular and humoral immunities. This study reports one such peptide, HCV‐core protein at positions 35–44, having HLA‐A2 binding motifs. IgG specific to this CTL‐epitope peptide is consistently detectable in a majority of the patients with HCV infection regardless of the different HLA types, different disease conditions, and different HCV‐genotypes tested. The sequence LPRR at positions 37–40 is considered to be the fine epitope recognized by the IgG. These results may provide new insights for the development of both therapeutic and diagnostic modalities of HCV at lower costs.

Therefore, the peptide at positions 30-39 of the core protein could be an appropriate target molecule of specific immunotherapy for all HLA-A11(+), -A31(+), and -A33(+) patients with HCV1b-related diseases.

We previously reported an unexpected phenomenon, i.e., several cancer vaccine peptides, including a cyclophilin B-derived peptide (CypB-84), elicited an immediate-type skin reaction in prevaccination skin tests. These peptides were prohibited in the subsequent vaccinations because of a possible induction of systemic anaphylaxis. In this study, we investigated mechanisms involved in the peptide-elicited inflammatory reactions in BALB/c mice whose MHC class I molecule (Kd) shared similar binding motifs with the human HLA-A24 molecule. Among 11 peptides tested, all of which had been scheduled for use in clinical trials with HLA-A24+ cancer patients, three peptides (CypB-84, ART1-170, and ART4-13) elicited immediate footpad reactions in BALB/c mice similar to the skin reactions in humans. The footpad reaction was also observed in C57BL/6, athymic nu/nu, and CB17-SCID mice, but not in mast cell-deficient WBB6F1w/wv mice, indicating the reaction was not mediated by specific immunity, but was mast cell-dependent. Furthermore, the reactions were not correlated to in vivo antitumor effects of the peptides. An anaphylaxis was not elicited when the peptides were systemically injected due to a very rapid clearance of the peptides from the plasma by in vivo degradation. These results suggest that certain peptides of cancer vaccine candidates exhibit an IgE-independent but mast cell-dependent inflammatory response with no elicitation of systemic anaphylaxis, and may provide new insights for further development of peptide-based vaccinations for cancer patients.