Therapeutic vaccination against a murine lymphoma by intratumoral injection of a cationic anticancer peptide
Therapeutic vaccination against a murine lymphoma by intratumoral injection of a cationic anticancer peptide
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DOI：
10.1007/s00262-010-0857-6
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发表时间：
2010-08-01
影响因子：
5.8
通讯作者：
Rekdal, Oystein
中科院分区：
文献类型：
--
作者：
Berge, Gerd;Eliassen, Liv Tone;Rekdal, Oystein
阳离子抗菌肽（CAPs）具有良好的抗癌活性。在本研究中，我们研究了从CAP牛乳铁蛋白（LfcinB）中提取的9聚肽LTX-302的体内抗肿瘤作用。采用皮下接种法在同基因小鼠中建立了起源于BALB/c的A20 B细胞淋巴瘤。在大多数动物瘤内注射LTX-302导致肿瘤坏死和炎症细胞浸润，随后肿瘤完全消退。这种效果依赖于T细胞，因为干预在裸鼠中是无效的。成功治疗的小鼠可以抵抗A20细胞的再攻击，但不能抵抗甲氧甲胺A肉瘤细胞。ltx -302处理小鼠脾脏细胞可过继转移肿瘤抗性。T淋巴细胞或CD4（+）或CD8(+) T细胞亚群的消耗消除了耐药性。综上所述，这些数据表明LTX-302治疗诱导了针对A20淋巴瘤的长期特异性细胞免疫，并且CD4（+）和CD8(+) T细胞都是必需的。因此，除了提供局部肿瘤控制外，肿瘤内给药裂解肽可能为治疗性癌症疫苗接种提供一种新的策略。
Cationic antimicrobial peptides (CAPs) exhibit promising anticancer activities. In the present study, we have examined the in vivo antitumoral effects of a 9-mer peptide, LTX-302, which is derived from the CAP bovine lactoferricin (LfcinB). A20 B cell lymphomas of BALB/c origin were established by subcutaneous inoculation in syngeneic mice. Intratumoral LTX-302 injection resulted in tumor necrosis and infiltration of inflammatory cells followed by complete regression of the tumors in the majority of the animals. This effect was T cell dependent, since the intervention was inefficient in nude mice. Successfully treated mice were protected against rechallenge with A20 cells, but not against Meth A sarcoma cells. Tumor resistance could be adoptively transferred with spleen cells from LTX-302-treated mice. Resistance was abrogated by depletion of T lymphocytes, or either the CD4(+) or CD8(+) T cell subsets. Taken together, these data suggest that LTX-302 treatment induced long-term, specific cellular immunity against the A20 lymphoma and that both CD4(+) and CD8(+) T cells were required. Thus, intratumoral administration of lytic peptide might, in addition to providing local tumor control, confer a novel strategy for therapeutic vaccination against cancer.