1区 · 医学
Article
作者: Forman, Juliet ; Redd, Robert A ; Sun, Jing ; Uduman, Mohamed ; Li, Shuqiang ; Livak, Kenneth J ; Olsen, Lars Rønn ; Hu, Zhuting ; Sarkizova, Siranush ; Rodig, Scott ; Zhang, Wandi ; Yoon, Charles H ; Liu, Jinyan ; Shukla, Sachet A ; Leet, Donna E ; Fritsch, Edward F ; Ott, Patrick A ; Holden, Rebecca ; Hacohen, Nir ; Lee, Patrick C ; Bachireddy, Pavan ; Luoma, Adrienne M ; Peter, Lauren ; Buchbinder, Elizabeth I ; Iorgulescu, J Bryan ; Giobbie-Hurder, Anita ; Elagina, Liudmila ; Olive, Oriol ; Keskin, Derin B ; Huang, Teddy ; Ciantra, Zoe ; Allesøe, Rosa L ; Wucherpfennig, Kai W ; Pentelute, Bradley L ; Gohil, Satyen H ; Neuberg, Donna ; Barouch, Dan H ; Wu, Catherine J ; Oliveira, Giacomo ; Pyrdol, Jason ; Shetty, Keerthi
Personal neoantigen vaccines have been envisioned as an effective approach to induce, amplify and diversify antitumor T cell responses. To define the long-term effects of such a vaccine, we evaluated the clinical outcome and circulating immune responses of eight patients with surgically resected stage IIIB/C or IVM1a/b melanoma, at a median of almost 4 years after treatment with NeoVax, a long-peptide vaccine targeting up to 20 personal neoantigens per patient ( NCT01970358 ). All patients were alive and six were without evidence of active disease. We observed long-term persistence of neoantigen-specific T cell responses following vaccination, with ex vivo detection of neoantigen-specific T cells exhibiting a memory phenotype. We also found diversification of neoantigen-specific T cell clones over time, with emergence of multiple T cell receptor clonotypes exhibiting distinct functional avidities. Furthermore, we detected evidence of tumor infiltration by neoantigen-specific T cell clones after vaccination and epitope spreading, suggesting on-target vaccine-induced tumor cell killing. Personal neoantigen peptide vaccines thus induce T cell responses that persist over years and broaden the spectrum of tumor-specific cytotoxicity in patients with melanoma.