Journal of Clinical and Cellular Immunology
Open Access

4-1BB as an immune target

4^th International Conference and Exhibition on Immunology

September 28-30, 2015 Crowne Plaza Houston River Oaks, Houston, TX, USA

Holbrook Kohrt

Stanford University, USA

Posters-Accepted Abstracts: J Clin Cell Immunol

Abstract :

Preclinical update on anti-CD137 Mab and Trastuzumab stimulation of natural killer cells with an anti-CD137 antibody enhances the efficacy of Trastuzumab, Cetuximab, and Rituximab in HER2-expressing breast cancer, EGFR+ head and neck cancer, and CD20+ lymphoma. My focus is on NK cells and translational research work that led from an initial in vitro observation to Phase 1 clinical studies. The starting observation was that primary human NK cells in the presence of a CD20-positive cell line and rituximab for 24 h upregulated CD137 (4-1BB) at their cell surface, and this upregulation was dependent on effective ADCC. The same observation was made with trastuzumab and cetuximab in the presence of HER-positive and EGFR-positive tumors, respectively. Using an agonistic anti-CD137 antibody, we demonstrate that triggering CD137 on NK cells enhanced the antitumor activity of rituximab, trastuzumab and cetuximab in vitro and in vivo. I will present various additional means to enhance ADCC by blocking inhibitory signals, such as CD47 on macrophages, IL-15 on monocytes or DCs, KIR or PD-1 on NK cells.

Biography :

Email: kohrt@stanford.edu