Breast Cancers Are Immunogenic: Immunologic Analyses and a Phase II Pilot Clinical Trial Using Mutation-Reactive Autologous Lymphocytes

• DOI: 10.1200/jco.21.02170
• Publication Date: 2022-02-01T20:59:27Z
• Authors: Nikolaos Zacharakis; Lutfi M. Huq; Samantha J. Seitter; Sanghyun P. Kim; Jared J. Gartner; Sivasish Sindiri; Victoria K. Hill; Yong F. Li; Biman C. Paria; Satyajit Ray; Billel Gasmi; Chyi-chia Lee; Todd D. Prickett; Maria R. Parkhurst; Paul F. Robbins; Michelle M. Langhan; Thomas E. Shelton; Anup Y. Parikh; Shoshana T. Levi; Jonathan M. Herna...; Chuong D. Hoang; Richard M. Sherry; James C. Yang; Steven A. Feldman; Stephanie L. Goff; Steven A. Rosenberg
• Keywords: Lymphocytes, Tumor-Infiltrating; Mutation; Humans; Breast Neoplasms; Female; Immunotherapy, Adoptive; Transplantation, Autologous; 3. Good health

PURPOSE Metastatic breast cancer (mBrCa) is most often an incurable disease with only modest responses to available immunotherapies. This study investigates the immunogenicity of somatic mutations in and explores therapeutic efficacy a pilot trial mutation-reactive tumor-infiltrating lymphocytes (TILs) patients metastatic disease. PATIENTS AND METHODS Forty-two mBrCa refractory previous lines treatment underwent surgical resection lesion(s), isolation TIL cultures, identification exomic nonsynonymous tumor mutations, immunologic screening for neoantigen reactivity. Clinically eligible appropriate reactivity were enrolled into one cohort ongoing phase II adoptive cell transfer selected neoantigen-reactive TIL, short course pembrolizumab (ClinicalTrials.gov identifier: NCT01174121 ). RESULTS TILs isolated grown culture from resected lesions all 42 mBrCa, median number 112 (range: 6-563) per patient identified. Twenty-eight (67%) contained that recognized at least immunogenic mutation (median: 3 neoantigens patient, range: 1-11), 13 demonstrated robust transfer. Eight remained clinically treatment, six on protocol enriched neoantigen-specific combination (≤ 4 doses). Objective regression was noted three patients, including complete response (now over 5.5 years) two partial (6 10 months). CONCLUSION Most generated natural immune targeting expressed products their mutations. Adoptive highly personalized experimental option shown be capable mediating objective this deserves further study.