Antitumor effects of systemic and local immunization with a CTL-directed peptide in combination with a local injection of OK-432.
Antitumor effects of systemic and local immunization with a CTL-directed peptide in combination with a local injection of OK-432.
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DOI：
10.1158/1078-0432.ccr-05-1293
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发表时间：
2006-02
期刊：
影响因子：
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通讯作者：
T. Ono;M. Harada;A. Yamada;Masahiro Tanaka;Y. Takao;Yasuaki Tanaka;T. Mine;K. Sakamoto;T. Nakashima;K. Itoh
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文献类型：
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作者：
T. Ono;M. Harada;A. Yamada;Masahiro Tanaka;Y. Takao;Yasuaki Tanaka;T. Mine;K. Sakamoto;T. Nakashima;K. Itoh
目的：肿瘤疫苗接种后，T细胞在肿瘤部位的积累对于激发体内抗肿瘤作用至关重要。在这项研究中，我们研究了全身和局部免疫CTL导向肽并结合瘤周注射链球菌制剂OK-432诱导的抗肿瘤作用和相关作用机制。实验设计和结果：人SART 3（315-323）肽具有诱导人白细胞抗原A24限制性CTL的潜力，其不仅具有与小鼠SART 3相同的氨基酸序列，而且具有与H-2K（d）分子结合的能力。因此，SART 3（315-323）肽可用作H-2（d）小鼠中的肿瘤抗原衍生肽。用SART 3（315-323）肽进行全身免疫以及随后肿瘤周围注射SART 3（315-323）肽和OK-432有效地在BALB/c小鼠中诱导肽特异性和结肠26癌反应性CTL。联合治疗抑制了s.c.的生长。结肠癌26例在联合治疗的小鼠中，CD 8（+）和CD 4（+）T细胞在肿瘤部位的积聚比其他方案治疗的小鼠更明显。此外，在用组合疗法治疗的小鼠中，对所施用的SART 3（315-323）肽反应的IgG水平增加。结论：这些结果表明，抗肿瘤作用可以通过联合治疗有效地诱导，所述联合治疗包括用CTL导向的肽进行全身和局部免疫以及局部注射OK-432。
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.