Toward Personalized Lymphoma Immunotherapy: Identification of Common Driver Mutations Recognized by Patient CD8+ T Cells

摘要: Purpose: A fundamental challenge in the era of next-generation sequencing (NGS) is to design effective treatments tailored mutational profiles tumors. Many newly discovered cancer mutations are difficult target pharmacologically; however, T-cell–based therapies may provide a valuable alternative owing exquisite sensitivity and specificity antigen recognition. To explore this concept, we assessed immunogenicity panel genes that common sites driver follicular lymphoma, an immunologically sensitive yet currently incurable disease. Experimental Design: Exon capture NGS were used interrogate tumor samples from 53 patients with lymphoma for 10 frequently mutated genes. For 13 patients, predicted mutant peptides proteins evaluated recognition by autologous peripheral blood T cells after vitro priming. Results: Mutations identified 1–5 81% (43/53) samples. Autologous, mutation-specific CD8 + 23% (3/13) cases. T-cell responses directed toward putative CREBBP MEF2B. Responding showed versus wild-type recognized expressing appropriate mutations. appeared be naive repertoire, as they found at low frequencies only single time points each patient. Conclusions: Patients harbor rare functionally competent specific recurrent Our results support concept using individualized immunotherapies targeting other malignancies. Clin Cancer Res; 22(9); 2226–36. ©2015 AACR .