Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Biochim Biophys Acta Rev Cancer. 2024 Sep;1879(5):189126. doi: 10.1016/j.bbcan.2024.189126. Epub 2024 Jun 6.
Neoantigen-based therapy is a promising approach that selectively activates the immune system of the host to recognize and eradicate cancer cells. Preliminary clinical trials have validated the feasibility, safety, and immunogenicity of personalized neoantigen-directed vaccines, enhancing their effectiveness and broad applicability in immunotherapy. While many ongoing oncological trials concentrate on neoantigens derived from mutations, these targets do not consistently provoke an immune response in all patients harboring the mutations. Additionally, tumors like ovarian cancer, which have a low tumor mutational burden (TMB), may be less amenable to mutation-based neoantigen therapies. Recent advancements in next-generation sequencing and bioinformatics have uncovered a rich source of neoantigens from non-canonical RNAs associated with transposable elements (TEs). Considering the substantial presence of TEs in the human genome and the proven immunogenicity of TE-derived neoantigens in various tumor types, this review investigates the latest findings on TE-derived neoantigens, examining their clinical implications, challenges, and unique advantages in enhancing tumor immunotherapy.
基于新抗原的治疗是一种很有前途的方法，它可以选择性地激活宿主的免疫系统，从而识别和清除癌细胞。初步的临床试验已经验证了个性化新抗原导向疫苗的可行性、安全性和免疫原性，增强了它们在免疫治疗中的有效性和广泛适用性。虽然许多正在进行的肿瘤学试验集中在源自突变的新抗原上，但这些靶点并不能始终在所有携带突变的患者中引发免疫反应。此外，像卵巢癌这样肿瘤突变负担 (TMB) 较低的肿瘤可能不太适合基于突变的新抗原治疗。新一代测序和生物信息学的最新进展揭示了与转座元件 (TE) 相关的非典型 RNA 中丰富的新抗原来源。考虑到 TEs 在人类基因组中的大量存在，以及 TE 衍生的新抗原在各种肿瘤类型中的已证实的免疫原性，本综述探讨了 TE 衍生新抗原的最新发现，研究了它们在增强肿瘤免疫治疗方面的临床意义、挑战和独特优势。
