中国科学技术大学Xuesi Chen和Wantong Song合作取得重要工作进展。他们研究提出，克服有限新抗原表位的“Hit-and-run”（“打了就跑”）疫苗策略实现了有效的广泛抗肿瘤反应。相关研究成果2024年2月1日在线发表于《科学通报》杂志上。

据介绍，新抗原癌症疫苗已经被认为是癌症治疗最有前景的手段之一。然而，为具有低肿瘤突变负担的肿瘤类型鉴定新抗原，继续限制新抗原疫苗的有效性。

研究人员提出了一种“打了就跑”的疫苗策略，该策略启动T细胞攻击用外源性“新抗原”修饰的肿瘤细胞。这种疫苗策略利用肽纳米疫苗在含有相同肽抗原的纳米载体，进行肿瘤特异性修饰后引发抗原特异性T细胞反应。

通过基质金属蛋白酶2（MMP-2）敏感接头与OVA_257-264肽偶联的聚（2-恶唑啉）（POx），可以在体内用OVA肽有效且选择性地修饰肿瘤细胞。然后，设计了含有OVA_257-264肽的基于POx的纳米疫苗，以引发OVA特异性T细胞反应。在这种“打了就跑”的疫苗系统的组合中，即使没有OVA抗原表达，也证明了有效的疫苗疗法适用于所有肿瘤类型。

总之，这种方法提供了一种有前途的、统一的疫苗策略，来对抗肿瘤突变负担低的肿瘤。

附：英文原文

Title: Hit-and-run vaccine system that overcomes limited neoantigen epitopes for efficient broad antitumor response

Author: anonymous

Issue&Volume: 2024/02/01

Abstract: Neoantigen cancer vaccines have been envisioned as one of the most promising means for cancer therapies. However, identifying neoantigens for tumor types with low tumor mutation burdens continues to limit the effectiveness of neoantigen vaccines. Herein, we proposed a “hit-and-run” vaccine strategy which primes T cells to attack tumor cells decorated with exogenous “neo-antigens”. This vaccine strategy utilizes a peptide nanovaccine to elicit antigen-specific T cell responses after tumor-specific decoration with a nanocarrier containing the same peptide antigens. We demonstrated that a poly(2-oxazoline)s (POx) conjugated with OVA257-264 peptide through a matrix metalloprotease 2 (MMP-2) sensitive linker could efficiently and selectively decorate tumor cells with OVA peptides in vivo. Then, a POx-based nanovaccine containing OVA257-264 peptides to elicit OVA-specific T cell responses was designed. In combination of this hit-and-run vaccine system, an effective vaccine therapy was demonstrated across tumor types even without OVA antigen expression. This approach provides a promising and uniform vaccine strategy against tumors with a low tumor mutation burden.

DOI: 10.1016/j.scib.2024.01.039

Source: https://www.sciencedirect.com/science/article/abs/pii/S2095927324000665