Neoadjuvant anti-OX40 (MEDI6469) therapy in patients with head and neck squamous cell carcinoma activates and expands antigen-specific tumor-infiltrating T cells

• DOI: 10.1038/s41467-021-21383-1
• Publication Date: 2021-02-17T18:37:58Z
• Authors: Rebekka Duhen; Carmen Ballestero...; Alexandra K. Frye; Eric Tran; Venkatesh Rajaman...; Shu-Ching Chang; Yoshinobu Koguchi; Carlo B. Bifulco; Brady Bernard; Rom S. Leidner; Brendan D. Curti; Bernard A. Fox; Walter J. Urba; R. Bryan Bell; Andrew D. Weinberg
• Keywords: Neoadjuvant Therapy; Tumor-infiltrating lymphocytes

Despite the success of checkpoint blockade in some cancer patients, there is an unmet need to improve outcomes. Targeting alternative pathways, such as costimulatory molecules (e.g. OX40, GITR, and 4-1BB), can enhance T cell immunity tumor-bearing hosts. Here we describe results from a phase Ib clinical trial (NCT02274155) which 17 patients with locally advanced head neck squamous carcinoma (HNSCC) received murine anti-human OX40 agonist antibody (MEDI6469) prior definitive surgical resection. The primary endpoint was determine safety feasibility anti-OX40 neoadjuvant treatment. secondary objective assess effect on lymphocyte subsets tumor blood. Neoadjuvant well tolerated did not delay surgery, thus meeting endpoint. Peripheral blood phenotyping data show increases CD4+ CD8+ proliferation two weeks after administration. Comparison biopsies before treatment reveals increase activated, conventional tumor-infiltrating lymphocytes (TIL) most higher clonality by TCRβ sequencing. Analyses TIL tumor-antigen reactive, proliferating CD103+ CD39+ cells 25% evaluable tissue (N = 4/16), all whom remain disease-free. These provide evidence that surgery safe activation tumor. Our work suggests tumor-reactive could serve potential biomarker activity.