David A. Braun; Giorgia Moranzoni; Vipheaviny Chea; Bradley A. McGregor; Eryn Blass; Chloe Ran Tu; Allison P. Vanasse; Cleo Forman; Juliet Forman; Alexander B. Afeyan; Nicholas Schindler; Yiwen Liu; Shuqiang Li; Jackson Southard; Steven L. Chang; Michelle S. Hirsch; Nicole R. LeBoeuf; Oriol Olive; Ambica Mehndiratta; Haley Greenslade; Keerthi Shetty; Susan Klaeger; Siranush Sarkizova; Christina B. Pedersen; Matthew Mossanen; Isabel Carulli; Anna Tarren; Joseph Duke-Cohan; Alexis A. Howard; J. Bryan Iorgulescu; Bohoon Shim; Jeremy M. Simon; Sabina Signoretti; Jon C. Aster; Liudmila Elagina; Steven A. Carr; Ignaty Leshchiner; Gad Getz; Stacey Gabriel; Nir Hacohen; Lars Rønn Olsen; Giacomo Oliveira; Donna Neuberg; Kenneth J. Livak; Sachet A. Shukla; Edward F. Fritsch; Catherine J. Wu; Derin B. Keskin; Patrick A. Ott; Toni K. Choueiri · 2025 · Nature
Paper
Personalized cancer vaccines (PCVs) can generate circulating immune responses against predicted neoantigens1–6. However, whether such responses can target cancer driver mutations, lead to immune recognition of a patient’s tumour and result in clinical activity are largely unknown. These questions are of particular interest for patients who have tumours with a low mutational burden. Here we conducted a phase I trial (ClinicalTrials.gov identifier NCT02950766) to test a neoantigen-targeting PCV in patients with high-risk, fully resected clear cell renal cell carcinoma (RCC; stage III or IV) with or without ipilimumab administered adjacent to the vaccine. At a median follow-up of 40.2 months after surgery, none of the 9 participants enrolled in the study had a recurrence of RCC. No dose-limiting toxicities were observed. All patients generated T cell immune responses against the PCV antigens, including to RCC driver mutations in VHL, PBRM1, BAP1, KDM5C and PIK3CA. Following vaccination, there was a durable expansion of peripheral T cell clones. Moreover, T cell reactivity against autologous tumours was detected in seven out of nine patients. Our results demonstrate that neoantigen-targeting PCVs in high-risk RCC are highly immunogenic, capable of targeting key driver mutations and can induce antitumour immunity. These observations, in conjunction with the absence of recurrence in all nine vaccinated patients, highlights the promise of PCVs as effective adjuvant therapy in RCC. A phase I trial of a neoantigen-targeting personalized cancer vaccine led to durable and polyfunctional T cell responses and antitumour recognition, and was associated with no recurrence in patients with high-risk clear cell renal cell carcinoma.
Analysis
A phase I trial demonstrated that a personalized neoantigen vaccine is highly immunogenic, targets driver mutations, and induces anti-tumor immunity in high-risk clear cell renal cell carcinoma patients, with no observed recurrences.
Discovery
Ruby Srivastava
Karthick Vasudevan; T Dhanushkumar; Sripad Rama Hebbar; Prasanna Kumar Selvam; Majji Rambabu; K. Anbarasu; Rohini Karunakaran
Dariush Haghmorad; Majid Eslami; Niloufar Orooji; Iryna Halabitska; Iryna Kamyshna; Oleksandr Kamyshnyi; Valentyn Oksenych
Zachary Sethna; Pablo Guasp; Charlotte Reiche; Martina Milighetti; Nicholas Ceglia; Erin Patterson; Jayon Lihm; George C. Payne; Olga Lyudovyk; Luis A. Rojas; Nan Pang; Akihiro Ohmoto; Masataka Amisaki; Abderezak Zebboudj; Zagaa Odgerel; Emmanuel M. Bruno; Siqi Linsey Zhang; C. K. Cheng; Yuval Elhanati; Evelyna Derhovanessian; Luisa Manning; Felicitas Müller; Ina Rhee; Mahesh Yadav; Taha Merghoub; Jedd D. Wolchok; Olca Baştürk; Mithat Gönen; Andrew S. Epstein; Parisa Momtaz; Wungki Park; Ryan Sugarman; Anna M. Varghese; Elizabeth Won; Avni M. Desai; Alice C. Wei; Michael I. D’Angelica; T. Peter Kingham; Kevin C. Soares; William R. Jarnagin; Jeffrey A. Drebin; Eileen M. O’Reilly; Ira Mellman; Uğur Şahin; Özlem Türeci; Benjamin D. Greenbaum; Vinod P. Balachandran
Ting Fan; Congcong Xu; Jichuan Wu; Yihua Cai; WuQiang Cao; Haifa Shen; Mingna Zhang; Hanfei Zhu; Jingxian Yang; Zhounan Zhu; Xiaopin Ma; Jiale Ren; Lei Huang; Qianyun Li; Yuying Tang; Bo Yu; Chunxiu Chen; Mingcheng Xu; Qiuhe Wang; Zhuya Xu; Fengjia Chen; Shujing Liang; Zhixian Zhong; Anmbreen Jamroze; Dean G. Tang; Hangwen Li; Chunyan Dong
Fei Wang; Cai Guang; Yingchao Wang; Qiuyu Zhuang; Zhixiong Cai; Yingying Li; Shaodong Gao; Fang Li; Cuilin Zhang; Bixing Zhao; Xiaolong Liu
Source record