A Study of the Humanized Monoclonal Antibody CT109 in Combination with FOLFIRI and Bortezomib as a Treatment for Colorectal Cancer
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Arias Cardenas, Kelly
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Abstract
Colorectal cancer ranks as the 2nd leading cause of cancer death in the United States. New drugs are urgently needed to increase the survival of patients with colorectal cancer. FOLFIRI is the most commonly used chemotherapy treatment in colorectal cancer, yet most patients develop side effects that severely affect quality of life. Bortezomib, an anti-cancer drug approved for multiple myeloma and lymphoma has been reported as an effective treatment in colorectal cancer that enhances apoptosis and attenuates tumor growth. Stromatis Pharma has developed a humanized monoclonal antibody, CT109, against CEACAM6 (new checkpoint inhibitor) that has demonstrated its promising antitumor activity against pancreatic and colorectal cancer in preclinical models. Monoclonal antibodies (moAbs) can be used in combination with drugs to treat cancer as adjunct therapy. MoAbs minimize treatment toxicity and are more effective at shrinking xi tumors, inhibiting tumor growth, prolonging life, and/or improving quality of life. The purpose of this study was to evaluate the functional capabilities of CT109 either alone or in combination with chemotherapy treatments. We used antibody-dependent cellular cytotoxicity (ADCC) assays, immunoblotting and cell viability assays as an in-vitro assessment of the CT109 efficacy in combination with chemotherapy drugs. Results show that the combination of CT109 with Bortezomib enhanced poly ADP ribose polymerase (PARP) cleavage and increased apoptosis in HT29 cells. Further, the synergistic inhibition and/or reduction of tumor growth, in combination with FOLFIRI, were observed in-vivo, in a colorectal adenocarcinoma tumor xenograft model in nu/nu mice. We found that the humanized monoclonal antibody CT109 enhanced the anti-cancer effect of both treatments. These data support the use of a novel monoclonal antibody, CT109 as an adjunct therapy to treat this deadly malignancy.
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FOLFIRI, Colorectal, Cancer, Bortezomib