丹娜-法伯癌症研究所Patrick A. Ott研究组报道了多佐剂个人新抗原疫苗在黑色素瘤中产生强效免疫。该项研究成果发表在2025年7月10日出版的《细胞》上。

由于抗原可用性和有效的T细胞启动对于最大的免疫原性至关重要，该团队在10名黑色素瘤患者中测试了一种合成长肽疫苗，该疫苗由Montanide、poly-ICLC和局部给药易普利姆单抗以及全身纳沃单抗组成。这些个体化疫苗在所有9名完全接种疫苗的患者中产生了针对大多数免疫新表位的体外T细胞反应，在9名患者中有6名产生了体外CD8⁺ T细胞反应。疫苗接种诱导了数百种循环和肿瘤内T细胞受体（TCR）克隆型，这些克隆型与PD-1抑制后产生的克隆型不同。通过将T细胞克隆型的疫苗新抗原特异性与肿瘤中的单细胞表型联系起来，小组证明了接种疫苗后肿瘤内T细胞库的重塑。这些观察结果表明，多管齐下的免疫佐剂可以增强T细胞对新抗原靶向疫苗的反应。

据介绍，个体化新抗原靶向疫苗已显示出巨大的前景；然而，仍然需要改进免疫原性。

附：英文原文

Title: A multi-adjuvant personal neoantigen vaccine generates potent immunity in melanoma

Author: Eryn Blass, Derin B. Keskin, Chloe R. Tu, Cleo Forman, Allison Vanasse, Haley E. Sax, Bohoon Shim, Vipheaviny Chea, Nawoo Kim, Isabel Carulli, Jackson Southard, Haoxiang Lyu, Wesley Lu, Micah Rickles-Young, Alexander B. Afeyan, Oriol Olive, Ambica Mehndiratta, Haley Greenslade, Keerthi Shetty, Joanna Baginska, Ilana Gomez Diaz, Allison Nau, Kathleen L. Pfaff, Andrew Gans, Srinika Ranasinghe, Elizabeth I. Buchbinder, Tamara A. Sussman, Megan L. Insco, Charles H. Yoon, Scott J. Rodig, Sachet A. Shukla, Shuqiang Li, Jon C. Aster, David A. Braun, Carrie Cibulskis, Nir Hacohen, Donna S. Neuberg, Anita Giobbie-Hurder, Kenneth J. Livak, Edward F. Fritsch, Giacomo Oliveira, Jeremy M. Simon, Catherine J. Wu, Patrick A. Ott

Issue&Volume: 2025-07-10

Abstract: Personalized neoantigen-targeting vaccines have demonstrated great promise; however, improved immunogenicity is still needed. Since antigen availability and effective T cell priming are critical for maximal immunogenicity, we tested a synthetic long peptide vaccine formulated with Montanide, poly-ICLC, and locally administered ipilimumab in addition to systemic nivolumab in 10 patients with melanoma. These personalized vaccines generated de novo ex vivo T cell responses against the majority of immunizing neoepitopes in all 9 fully vaccinated patients and ex vivo CD8+ T cell responses in 6 of 9. Vaccination induced hundreds of circulating and intratumoral T cell receptor (TCR) clonotypes that were distinct from those arising after PD-1 inhibition. By linking the vaccine neoantigen specificity of T cell clonotypes with single-cell phenotypes in tumors, we demonstrate remodeling of the intratumoral T cell repertoire following vaccination. These observations show that multi-pronged immune adjuvanticity can boost T cell responses to neoantigen-targeting vaccines.

DOI: 10.1016/j.cell.2025.06.019

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00685-3