Llopiz Diana, Dotor Javier, Zabaleta Aintzane, Lasarte Juan J, Prieto Jesús, Borrás-Cuesta Francisco, Sarobe Pablo
Center for Applied Medical Research (CIMA), Division of Hepatology and Gene Therapy, University of Navarra, Pío XII 55, 31008, Pamplona, Spain.
Cancer Immunol Immunother. 2008 Jan;57(1):19-29. doi: 10.1007/s00262-007-0346-8. Epub 2007 Jun 13.
The low immunogenicity of malignant cells is one of the causes responsible for the lack of antitumor immune responses. Thus, development of new therapeutic strategies aimed at enhancing presentation of tumor antigens to T cells is a main goal of cancer immunotherapy. With this aim, we studied the efficacy of administering adjuvants poly(I:C) and agonistic anti-CD40 antibody plus a tumor antigen. Joint intravenous immunization with these adjuvants and a model tumor antigen (ovalbumin) was able to synergistically induce potent and long lasting antitumor T-cell responses. These responses protected against challenge with E.G7-OVA tumor cells in prophylactic short- and long-term vaccination. In a therapeutic setting, repeated intratumor administration of adjuvants plus antigen was able to reject established tumors in all treated animals, leading in some cases to the rejection of both locally treated and untreated tumors. Antitumor immune responses induced by these protocols were mediated not only by T-cells but also by NK cells. In conclusion, combined administration of adjuvants poly(I:C) and anti-CD40 plus a tumor antigen is an efficient strategy for prophylactic and therapeutic antitumor vaccination.
恶性细胞的低免疫原性是导致缺乏抗肿瘤免疫反应的原因之一。因此，开发旨在增强肿瘤抗原向T细胞呈递的新治疗策略是癌症免疫治疗的主要目标。出于这个目的，我们研究了给予佐剂聚肌胞苷酸（poly(I:C)）和激动性抗CD40抗体加肿瘤抗原的疗效。用这些佐剂与一种模型肿瘤抗原（卵清蛋白）进行联合静脉免疫能够协同诱导强效且持久的抗肿瘤T细胞反应。在预防性短期和长期疫苗接种中，这些反应可抵御E.G7 - OVA肿瘤细胞的攻击。在治疗环境中，向肿瘤内反复给予佐剂加抗原能够使所有接受治疗的动物体内已形成的肿瘤消退，在某些情况下还能导致局部治疗和未治疗的肿瘤均被清除。这些方案诱导的抗肿瘤免疫反应不仅由T细胞介导，也由自然杀伤细胞介导。总之，联合给予佐剂聚肌胞苷酸（poly(I:C)）和抗CD40加肿瘤抗原是一种用于预防性和治疗性抗肿瘤疫苗接种的有效策略。
