Cardiovascular Institute, School of Medicine, Stanford University, Stanford, CA, United States.
Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Stanford, CA, United States.
Front Immunol. 2019 Jul 8;10:1510. doi: 10.3389/fimmu.2019.01510. eCollection 2019.
Over a century ago, it was reported that immunization with embryonic/fetal tissue could lead to the rejection of transplanted tumors in animals. Subsequent studies demonstrated that vaccination of embryonic materials in animals induced cellular and humoral immunity against transplantable tumors and carcinogen-induced tumors. Therefore, it has been hypothesized that the shared antigens between tumors and embryonic/fetal tissues (oncofetal antigens) are the key to anti-tumor immune responses in these studies. However, early oncofetal antigen-based cancer vaccines usually utilize xenogeneic or allogeneic embryonic stem cells or tissues, making it difficult to tease apart the anti-tumor immunity elicited by the oncofetal antigens vs. graft-vs.-host responses. Recently, one oncofetal antigen-based cancer vaccine using autologous induced pluripotent stem cells (iPSCs) demonstrated marked prophylactic and therapeutic potential, suggesting critical roles of oncofetal antigens in inducing anti-tumor immunity. In this review, we present an overview of recent studies in the field of oncofetal antigen-based cancer vaccines, including single peptide-based cancer vaccines, embryonic stem cell (ESC)- and iPSC-based whole-cell vaccines, and provide insights on future directions.
一个多世纪以前,有报道称胚胎/胎儿组织免疫接种可导致动物移植肿瘤的排斥。随后的研究表明,动物胚胎材料的接种可诱导针对可移植肿瘤和致癌剂诱导肿瘤的细胞和体液免疫。因此,有人假设肿瘤和胚胎/胎儿组织之间的共同抗原(oncofetal 抗原)是这些研究中抗肿瘤免疫反应的关键。然而,早期基于oncofetal 抗原的癌症疫苗通常使用异种或同种异体胚胎干细胞或组织,因此很难区分由 oncofetal 抗原引起的抗肿瘤免疫与移植物抗宿主反应。最近,一种使用自体诱导多能干细胞(iPSCs)的基于 oncofetal 抗原的癌症疫苗显示出显著的预防和治疗潜力,表明 oncofetal 抗原在诱导抗肿瘤免疫中起关键作用。在这篇综述中,我们介绍了基于 oncofetal 抗原的癌症疫苗领域的最新研究进展,包括基于单一肽的癌症疫苗、胚胎干细胞(ESC)和 iPSC 为基础的全细胞疫苗,并提供了对未来方向的见解。