Vaccination against Nonmutated Neoantigens Induced in Recurrent and Future Tumors

• Published in: Cancer immunology research Vol. 8; no. 7; p. 856
• Main Authors: Garrido, Greta, Schrand, Brett, Levay, Agata, Rabasa, Ailem, Ferrantella, Anthony, Da Silva, Diane M, D'Eramo, Francesca, Marijt, Koen A, Zhang, Zhuoran, Kwon, Deukwoo, Kortylewski, Marcin, Kast, W Martin, Dudeja, Vikas, van Hall, Thorbald, Gilboa, Eli
• Format: Journal Article
• Language: English
• Published: United States 01.07.2020
• Subjects: Animals; Antigen Presentation - immunology; Antigens, Neoplasm - immunology; ATP-Binding Cassette Transporters - antagonists & inhibitors; ATP-Binding Cassette Transporters - immunology; Cancer Vaccines - administration & dosage; Cancer Vaccines - immunology; CD8-Positive T-Lymphocytes - immunology; Cell Line, Tumor; Disease Models, Animal; Female; Humans; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasm Recurrence, Local - immunology; Neoplasm Recurrence, Local - therapy; Neoplasms - immunology; Neoplasms - therapy; RNA, Small Interfering - genetics
• ISSN: 2326-6074
• DOI: 10.1158/2326-6066.CIR-20-0020

Vaccination of patients against neoantigens expressed in concurrent tumors, recurrent tumors, or tumors developing in individuals at risk of cancer is posing major challenges in terms of which antigens to target and is limited to patients expressing neoantigens in their tumors. Here, we describe a vaccination strategy against antigens that were induced in tumor cells by downregulation of the peptide transporter associated with antigen processing (TAP). Vaccination against TAP downregulation-induced antigens was more effective than vaccination against mutation-derived neoantigens, was devoid of measurable toxicity, and inhibited the growth of concurrent and future tumors in models of recurrence and premalignant disease. Human CD8 T cells stimulated with TAP dendritic cells elicited a polyclonal T-cell response that recognized tumor cells with experimentally reduced TAP expression. Vaccination against TAP downregulation-induced antigens overcomes the main limitations of vaccinating against mostly unique tumor-resident neoantigens and could represent a simpler vaccination strategy that will be applicable to most patients with cancer.