An immunogenic personal neoantigen vaccine for patients with melanoma

The results of a phase I trial assessing a personal neoantigen multi-peptide vaccine in patients with melanoma, showing feasibility, safety, and immunogenicity. Personalized cancer vaccine trials Neoantigens have long been considered optimal targets for anti-tumour vaccines, and recent mutation codi...

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Veröffentlicht in:Nature (London) 2017-07, Vol.547 (7662), p.217-221
Hauptverfasser: Ott, Patrick A., Hu, Zhuting, Keskin, Derin B., Shukla, Sachet A., Sun, Jing, Bozym, David J., Zhang, Wandi, Luoma, Adrienne, Giobbie-Hurder, Anita, Peter, Lauren, Chen, Christina, Olive, Oriol, Carter, Todd A., Li, Shuqiang, Lieb, David J., Eisenhaure, Thomas, Gjini, Evisa, Stevens, Jonathan, Lane, William J., Javeri, Indu, Nellaiappan, Kaliappanadar, Salazar, Andres M., Daley, Heather, Seaman, Michael, Buchbinder, Elizabeth I., Yoon, Charles H., Harden, Maegan, Lennon, Niall, Gabriel, Stacey, Rodig, Scott J., Barouch, Dan H., Aster, Jon C., Getz, Gad, Wucherpfennig, Kai, Neuberg, Donna, Ritz, Jerome, Lander, Eric S., Fritsch, Edward F., Hacohen, Nir, Wu, Catherine J.
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Zusammenfassung:The results of a phase I trial assessing a personal neoantigen multi-peptide vaccine in patients with melanoma, showing feasibility, safety, and immunogenicity. Personalized cancer vaccine trials Neoantigens have long been considered optimal targets for anti-tumour vaccines, and recent mutation coding and prediction techniques have aimed to streamline their identification and selection. Two papers in this issue report results from personalized neoantigen vaccine trials in patients with cancer. Catherine Wu and colleagues report the results of a phase I trial of a personalized cancer vaccine that targets up to 20 patient neoantigens. The vaccine was safe and induced tumour-antigen-specific immune responses. Four out of six patients treated showed no recurrence at 25 months, and progressing patients responded to further therapy with checkpoint inhibitor. Ugur Sahin and colleagues report the first-in-human application of a personalized neoantigen vaccine in patients with melanoma. Their vaccination strategy includes sequencing and computational identification of neoantigens from patients, and design and manufacture of a poly-antigen RNA vaccine for treatment. In 13 patients, the vaccine boosted immunity against some of the selected tumour antigens from the individual patients, and two patients showed infiltration of tumour-reactive T cells. These results suggest that personalized vaccines could be refined and tailored to provide clinical benefit as cancer immunotherapies. Effective anti-tumour immunity in humans has been associated with the presence of T cells directed at cancer neoantigens 1 , a class of HLA-bound peptides that arise from tumour-specific mutations. They are highly immunogenic because they are not present in normal tissues and hence bypass central thymic tolerance. Although neoantigens were long-envisioned as optimal targets for an anti-tumour immune response 2 , their systematic discovery and evaluation only became feasible with the recent availability of massively parallel sequencing for detection of all coding mutations within tumours, and of machine learning approaches to reliably predict those mutated peptides with high-affinity binding of autologous human leukocyte antigen (HLA) molecules. We hypothesized that vaccination with neoantigens can both expand pre-existing neoantigen-specific T-cell populations and induce a broader repertoire of new T-cell specificities in cancer patients, tipping the intra-tumoural balance in favour of enhan
ISSN:0028-0836
1476-4687
DOI:10.1038/nature22991