Salem Mohamed L
Immunology and Biotechnology Unit, Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt.
Methods Mol Biol. 2014;1139:479-503. doi: 10.1007/978-1-4939-0345-0_37.
Effective antitumor immunity requires the generation and persistence of functional tumor-specific T-cell responses. Among the critical factors that often control these responses is how the antigen is delivered and presented to T cells. The use of peptide-based vaccination has been found to be a promising means to induce antitumor T-cell responses but with limited effects even if the peptide is co-delivered with a potent adjuvant. This limited response could be due to cancer-induced dysfunction in dendritic cells (DC), which play a central role in shaping the quantity and quality of antitumor immunity. Therefore, DC-based peptide delivery of tumor antigen is becoming a potential approach in cancer immunotherapy. In this approach, autologous DC are generated from their precursors in bone marrow or peripheral blood mononuclear cells, loaded with tumor antigen(s) and then infused back to the tumor-bearing host in about 7 days. This DC-based vaccination can act as an antigen delivery vehicle as well as a potent adjuvant, resulting in measurable antitumor immunity in several cancer settings in preclinical and clinical studies. This chapter focuses on DC-based vaccination and how this approach can be more efficacious in cancer immunotherapy.Effective antitumor immunity requires the generation and persistence of functional tumor-specific T-cell responses. Among the critical factors that often control these responses is how the antigen is delivered and presented to T cells. The use of peptide-based vaccination has been found to be a promising means to induce antitumor T-cell responses but with limited effects even if the peptide is co-delivered with a potent adjuvant. This limited response could be due to cancer-induced dysfunction in dendritic cells (DC), which play a central role in shaping the quantity and quality of antitumor immunity. Therefore, DC-based peptide delivery of tumor antigen is becoming a potential approach in cancer immunotherapy. In this approach, autologous DC are generated from their precursors in bone marrow or peripheral blood mononuclear cells, loaded with tumor antigen(s) and then infused back to the tumor-bearing host in about 7 days. This DC-based vaccination can act as an antigen delivery vehicle as well as a potent adjuvant, resulting in measurable antitumor immunity in several cancer settings in preclinical and clinical studies. This chapter focuses on DC-based vaccination and how this approach can be more efficacious in cancer immunotherapy.
有效的抗肿瘤免疫需要产生并持续存在功能性肿瘤特异性T细胞反应。在常常控制这些反应的关键因素中，抗原如何递呈给T细胞是其中之一。基于肽的疫苗接种已被发现是诱导抗肿瘤T细胞反应的一种有前景的方法，但即便该肽与强效佐剂共同递送，效果仍有限。这种有限的反应可能是由于癌症导致树突状细胞（DC）功能障碍，而树突状细胞在塑造抗肿瘤免疫的数量和质量方面起着核心作用。因此，基于DC的肿瘤抗原肽递送正成为癌症免疫治疗中的一种潜在方法。在这种方法中，自体外周血单核细胞或骨髓中的前体细胞生成DC，用肿瘤抗原负载，然后在大约7天后回输到荷瘤宿主。这种基于DC的疫苗接种既可以作为抗原递送载体，也可以作为强效佐剂，在临床前和临床研究的多种癌症环境中都能产生可测量的抗肿瘤免疫。本章重点介绍基于DC的疫苗接种以及该方法如何在癌症免疫治疗中更有效。有效的抗肿瘤免疫需要产生并持续存在功能性肿瘤特异性T细胞反应。在常常控制这些反应的关键因素中，抗原如何递呈给T细胞是其中之一。基于肽的疫苗接种已被发现是诱导抗肿瘤T细胞反应的一种有前景的方法，但即便该肽与强效佐剂共同递送，效果仍有限。这种有限的反应可能是由于癌症导致树突状细胞（DC）功能障碍，而树突状细胞在塑造抗肿瘤免疫的数量和质量方面起着核心作用。因此，基于DC的肿瘤抗原肽递送正成为癌症免疫治疗中的一种潜在方法。在这种方法中，自体外周血单核细胞或骨髓中的前体细胞生成DC，用肿瘤抗原负载，然后在大约7天后回输到荷瘤宿主。这种基于DC的疫苗接种既可以作为抗原递送载体，也可以作为强效佐剂，在临床前和临床研究的多种癌症环境中都能产生可测量的抗肿瘤免疫。本章重点介绍基于DC的疫苗接种以及该方法如何在癌症免疫治疗中更有效。
