Apomab, a fully human agonistic DR5
monoclonal antibody, triggers apoptosis through activation of the extrinsic apoptotic signaling pathway. In this study, we assessed the cytotoxic effect of
Apomab in vitro and evaluated its antitumor activity in murine models of
breast cancer development and progression. MDA-MB-231-TXSA
breast cancer cells were transplanted into the mammary fat pad or directly into the tibial marrow cavity of nude mice.
Apomab was administered early, postcancer
cell transplantation, or after
tumors progressed to an advanced stage.
Tumor burden was monitored progressively using bioluminescence imaging, and the development of
breast cancer-induced
osteolysis was measured using microcomputed tomography. In vitro,
Apomab treatment induced apoptosis in a panel of
breast cancer cell lines but was without effect on normal human primary osteoblasts, fibroblasts, or mammary epithelial cells. In vivo,
Apomab exerted remarkable
tumor suppressive activity leading to complete regression of well-advanced mammary
tumors. All animals transplanted with
breast cancer cells directly into their tibiae developed large osteolytic lesions that eroded the cortical bone. In contrast, treatment with
Apomab following an early treatment protocol inhibited both intraosseous and extraosseous
tumor growth and prevented
breast cancer-induced
osteolysis. In the
delayed treatment protocol,
Apomab treatment resulted in the complete regression of advanced tibial
tumors with progressive restoration of both trabecular and cortical bone leading to full resolution of osteolytic lesions.
Apomab represents a potent immunotherapeutic agent with strong activity against the development and progression of
breast cancer and should be evaluated in patients with primary and metastatic disease.