Introduction
Gastric cancer, cancer, adenocarcinoma, cancer death
GASTRIC CANCER, CANCER, CYTOTOXICITY, ADENOCARCINOMA
Gastric cancer is the fifth most common cancer and the fourth most common cause of cancer death globally (Sung et al. Zolbetuximab (previously known as IMAB362) is a first-in-development monoclonal IgG1 antibody against splice variant 2 of claudin 18 (CLDN18.2). Claudin family members are tight junction proteins, which establish cell polarity and regulate cellular permeability in epithelial cells (Rendon-Huerta et al. Zolbetuximab exerts its antitumor activity by antigen-specific activation of immune effector mechanisms and induces both antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) (Singh et al. We hypothesized that compounds that activate and expand γδ lymphocytes could augment zolbetuximab-mediated ADCC. The bisphosphonate zoledronic acid (ZA) is known to induce diverse immunological effects, including activation of cytolytic γ9δ2 T cells and NK cells (Lang et al. We evaluated zolbetuximab in combination with ZA and IL-2 in patients with advanced or metastatic G/GEJ adenocarcinoma to determine activation and kinetic profiles of immune cell populations induced by ZA with or without IL-2.