Title
An empirical antigen selection method identifies neoantigens that either elicit broad anti-tumor T cell responses or drive tumor growth.
Document Type
Article
Publication Date
1-27-2021
Publication Title
Cancer Discov
Keywords
california; JWCI
Abstract
Neoantigens are critical targets of anti-tumor T cell responses. The ATLAS{trade mark, serif} bioassay was developed to identify neoantigens empirically by expressing each unique patient-specific tumor mutation individually in E. coli, pulsing autologous dendritic cells in an ordered array, and testing the patient's T cells for recognition in an overnight assay. Profiling of T cells from lung cancer patients revealed both stimulatory and inhibitory responses to individual neoantigens. In the murine B16F10 melanoma model, therapeutic immunization with ATLAS-identified stimulatory neoantigens protected animals, whereas immunization with peptides associated with inhibitory ATLAS responses resulted in accelerated tumor growth and abolished efficacy of an otherwise-protective vaccine. A planned interim analysis of a clinical study testing a poly-ICLC adjuvanted personalized vaccine containing ATLAS-identified stimulatory neoantigens showed that it is well-tolerated. In an adjuvant setting, immunized patients generated both CD4+ and CD8+ T cell responses, with immune responses to 99% of the vaccinated peptide antigens.
Clinical Institute
Cancer
Department
Oncology
Department
Hematology
Recommended Citation
Lam, Hubert; McNeil, Lisa K; Starobinets, Hanna; DeVault, Victoria L; Cohen, Roger B; Twardowski, Przemyslaw; Johnson, Melissa L; Gillison, Maura L; Stein, Mark N; Vaishampayan, Ulka N; DeCillis, Arthur P; Foti, James J; Vemulapalli, Vijetha; Tjon, Emily; Ferber, Kyle; DeOliveira, Daniel B; Broom, Wendy; Agnihotri, Parul; Jaffee, Elizabeth M; Wong, Kwok-Kin; Drake, Charles G; Carroll, Pamela M; Davis, Thomas A; and Flechtner, Jessica Baker, "An empirical antigen selection method identifies neoantigens that either elicit broad anti-tumor T cell responses or drive tumor growth." (2021). Articles, Abstracts, and Reports. 4288.
https://digitalcommons.providence.org/publications/4288