On April 18, 2016 ChemoCentryx, Inc., (Nasdaq:CCXI), a clinical-stage biopharmaceutical company developing orally-administered therapeutics to treat autoimmune diseases, inflammatory disorders, and cancer, reported the presentation of data from its immuno-oncology program at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2016 Annual Meeting, being held April 16-20, 2016 in New Orleans, Louisiana (Press release, ChemoCentryx, APR 18, 2016, View Source [SID:1234510968]). The preclinical data highlight the synergistic effect of employing an antibody against the checkpoint inhibitor PD-L1 in conjunction with CCX9588, in a model of triple negative breast cancer. CCX9588 is a small molecule inhibitor of the chemokine receptor known as CCR1 and is currently in preclinical development for certain oncology indications targeting both solid and liquid tumors.
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The preclinical results were presented in a poster titled, "Combination therapy of chemokine receptor inhibition plus PD-L1 blockade potentiates anti-tumor effects in a murine model of breast cancer" (Abstract #3298, April 17, 1:00 to 5:00 p.m. ET, Session: Immune Modulating Agents 1, Convention Center, Halls G-J, Poster Section 26).
The presentation from the Company’s ongoing preclinical research investigating the effects of combining CCX9588 with an anti-PD-L1 antibody includes the following results and data:
The combination of CCX9588 and the anti-PD-L1 antibody ("Combination Treatment") significantly decreased circulating and tumor infiltrating granulocytic myeloid-derived suppressor cells, or G-MDSC’s.
G-MDSCs are known to be responsible for the induction of an immunosuppressive environment around the growing tumor, as well as a metastatic phenotype in primary tumors which can lead to the early dissemination of cancer cells.
G-MDSCs were demonstrated to be attracted by chemokines produced by the breast cancer cells, and directed migration of the G-MDSCs were shown to be specifically blocked by inhibiting CCR1 with CCX9588.
Combination Treatment increased the number of effector T cells in the tumor infiltrate, which is known to have an anti-cancer effect.
Overall tumor size and progression was also significantly reduced by the Combination Treatment.
"These results suggest that an orally-administered CCR1 inhibitor, such as CCX9588, combined with an antibody against the checkpoint inhibitor PD-L1, may be of utility in treating triple negative breast cancer, which we modeled in these experiments," said Pirow Bekker, MD, PhD, Chief Medical Officer, ChemoCentryx. "These data reveal an important role for the chemokine receptor CCR1 in modulating the suppressive nature of the tumor microenvironment, and suggest that blocking CCR1 could significantly help to unleash the potential of the body’s own immune system to attack cancer."
About the ChemoCentryx Immuno-Oncology Program
Myeloid derived suppressor cells (MDSCs) are thought to possess an immunosuppressive behavior, effectively helping tumors hide from the body’s natural cytotoxic immune response to tumor cells. These cells are thought to express chemokine receptors such CCR1 and CCR2 and are guided to the tumor microenvironment by the action of these receptors. Inhibiting CCR1 and CCR2 may lead to a reduction of MDSCs in the tumor microenvironment, and the concomitant liberation of the cytotoxic immune response against tumor cells, reduced tumor burden, and potentially lead to improved patient survival.
The Company currently has an ongoing clinical trial of CCX872, an inhibitor of the chemokine receptor known as CCR2, in patients with non-resectable pancreatic cancer. In addition, the Company is conducting preclinical research with various chemokine receptor inhibitors in combination with checkpoint inhibitors, such as those inhibiting the PD-L1 pathway, which may result in a greater anti-tumor effect than with checkpoint inhibition alone. CCX9588 is a small molecule inhibitor of CCR1 and is currently in preclinical development for certain oncology indications targeting both solid and liquid tumors.