"Unique neoantigens arise from somatic mutations in patients with gastrointestinal cancers"
Running title: Neoantigens in patients with gastrointestinal cancers
[The bold-faced highlight below is the Ziopharm trial that is about to begin.]
First published online June 4, 2019
Maria R. Parkhurst1 , Paul F. Robbins1 , Eric Tran2 , Todd D. Prickett1 , Jared J. Gartner1 , Li Jia1 , Gabriel Ivey1 , Yong F. Li1 , Mona El-Gamil1 , Almin Lalani1 , Jessica S. Crystal1 , Abraham Sachs1 , Eric Groh1 , Satyajit Ray1 , Lien T. Ngo1 , Scott Kivitz1 , Anna Pasetto1 , Rami Yossef1 , Frank J. Lowery1 , Stephanie L. Goff1 , Winifred Lo1 , Gal Cafri1 , Drew C. Deniger1 , Parisa Malekzadeh1 , Mojgan Ahmadzadeh1 , John R. Wunderlich1 , Robert P.T. Somerville1 , and Steven A. Rosenberg1
From the paper:
"The primary goal of the work presented here was to determine if patients with common
epithelial cancers harbor T lymphocytes that can specifically recognize proteins encoded by somatic mutations uniquely expressed by autologous tumor cells. By evaluating TIL fragment cultures from 75 consecutive patients, we identified neoantigen reactive T cells in 83% of patients with common gastrointestinal cancers, and 99% of the neoantigenic determinants appeared to be unique to the autologous patient. Although we observed a few objective clinical responses after treating patients with autologous TIL, we cannot draw any conclusions about the clinical efficacy of targeting neoantigens until we conduct clinical trials in which patients are treated with highly enriched populations of such T cells or with T cells genetically modified to express high levels and percentages of neoantigen reactive TCRs. Nonetheless, our observations demonstrate that most epithelial cancers, generally considered to be non-immunogenic, do elicit in vivo immune reactions and provide a rationale for developing new personalized cellbased immunotherapeutic treatments for patients with common epithelial cancers by targeting the unique tumor associated mutations expressed by those cancers."