JNJ-70218902 is a bispecific antibody capable of binding to tumor cells expressing TMEFF2 and CD3 on T cells. It induces an exposure-dependent pro-inflammatory response and targeted tumor cell lysis, and enhances T cell-mediated tumor cell killing (EC50: 1.4 nM). JNJ-70218902 holds significant potential for prostate cancer research.

JNJ-70218902 binds to TMEFF2-positive LNCaP-AR cells with an EC50 of 9.6 nM and shows no binding to TMEFF2-negative DU145 prostate cancer cells. It has a binding affinity to primary human T-cell CD3 with a KD of 151 nM. When co-incubated at a 3:1 effector-to-target ratio with healthy human donor T-cells and LNCaP-AR cells, JNJ-70218902 can induce T-cell-mediated cytotoxicity with an EC50 of 1.4 nM. Additionally, it increases cell surface CD8+ CD25+ expression and pro-inflammatory cytokine levels, indicating T-cell activation. JNJ-70218902 exhibits low cytotoxicity in DU145 cells.

JNJ-70218902 demonstrates antitumor activity in T cell-humanized NSG mice with LNCaP xenografts, showing a tumor growth inhibition rate of 75-122%, and in patient-derived LuCaP 86.2 xenografts with a tumor growth inhibition rate of 72-88%, when administered at concentrations up to 5 mg/kg. In a cynomolgus monkey model of prostate cancer, JNJ-70218902, administered at 0.075 mg/kg or escalated to 0.3 mg/kg after one week, induces activated and proliferating T cells and infiltrating inflammatory cells in the prostate, thereby mediating an effective immune response.