Potent immunomodulatory effects of the trifunctional antibody catumaxomab
Menée in vitro, cette étude française analyse les effets immunomodulateurs du catumaxomab sur les leucocytes infiltrant les ascites malignes
Catumaxomab (CatmAb), a trifunctional bispecific antibody directed against the epithelial cell adhesion molecule (EpCAM) and the T cell antigen CD3, is approved as intraperitoneal therapy for the treatment of malignant ascites in patients with EpCAM positive carcinomas. The immunomonitoring results of a Phase II/III study using CatmAb reported tumoricidal effect, associated with reduced VEGF levels, CD69 expressing T cells and the release of Th1 cytokines (1). Here, we comprehensively dissected the immunomodulatory effects of the CatmAb on the major subsets of malignant ascites- infiltrating leukocytes (TILs) and the molecular fingerprint of tumor cell death. We show that in the presence of EpCAM-positive tumor targets CatmAb markedly enhanced T cell activation (CD69, CD107A (LAMP1), HLA-DR and PD-1(PDCD1) expression), stimulated inflammatory CD4+Th1 and CD8+ Th1 to release IFNgamma but failed to trigger Th17 cells. Engagement of CD16-expressing cells caused upregulation of TRAIL (TNFSF10) and costimulatory CD40 and CD80 molecules. CatmAb promoted tumor cell death associated with ATP release and strongly synergized with oxaliplatin for the exposure of the three hallmarks of immunogenic cell death (calreticulin, HMGB1 and ATP). These findings warrant validation as potential biomarkers of efficacy of CatmAb.