Tumor Immunotherapy Efficacy Increased in Both Breast and Prostate Cancer Preclinical Models with Addition of Galectin Inhibitor
By a News Reporter-Staff News Editor at Cancer Vaccine Week -- Galectin Therapeutics (NASDAQ: GALT), the leading developer of therapeutics that target galectin proteins to treat fibrosis and cancer, announced that preclinical studies have shown that combining the galectin inhibitor GR-MD-02 with monoclonal antibodies that function as immune checkpoint blockade inhibitors enhance shrinkage of prostate and breast cancer tumors. These data were generated by the laboratory of Dr. William Redmond of the Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute (EACRI) at Providence Cancer Center (Portland, OR), an expert in tumor immunology and part of a comprehensive pre-clinical and clinical program in cancer immunotherapy. The addition of GR-MD-02, a drug that inhibits galectin proteins, was found to increase tumor shrinkage and enhance survival in immune competent mice with prostate and breast cancers when combined with one of the immune checkpoint blockade inhibitors, anti-CTLA-4 or anti-PD-1 (see also Galectin Therapeutics Inc.).
"Immunotherapy with checkpoint blockade inhibitors, such as anti-CTLA-4 monoclonal antibodies (marketed as YERVOY" by Bristol-Myers Squibb (BMS)) and anti-PD-1 monoclonal antibodies (in development at BMS and Merck), is an extremely exciting area for advancing human cancer immunotherapy," said Dr. Peter G. Traber, President, Chief Executive Officer and Chief Medical Officer, Galectin Therapeutics. "However, these agents are currently only effective in a limited percentage of patients. The ability of GR-MD-02 to increase the effectiveness of these important drugs is a potentially important approach to enhance cancer immunotherapy."
"The findings of these experiments show that GR-MD-02 had a robust effect on augmenting the immune response and tumor efficacy when combined with well characterized agents for cancer immunotherapy," said Dr. Redmond, Assistant Member at the EACRI. "The experimental tumor models used are relatively resistant to therapy to checkpoint blockade inhibitors alone, indicating that the addition of GR-MD-02 may be a potentially important agent in combination therapy."
"We have determined that these pre-clinical results are compelling for clinical translation and we are planning to seek FDA agreement to open a trial using YERVOY" (ipilimumab, anti-CTLA-4 mAb, BMS) in combination with GR-MD-02 in patients with advanced melanoma," said Brendan Curti, MD, Medical Oncologist and Director of the Providence Biotherapy Program at EACRI. "We are in the process of designing such a trial with Galectin Therapeutics."
Initial data was reported at the Tumor Immunology Keystone Conference in March of 2013 which showed that treatment with GR-MD-02 augmented CD8+ T-cell function in mice (poster available on Galectin web site: http://bit.ly/19gmjHX) These data show that in response to vaccination with an antigenic protein, inhibition of extracellular galectin-3 with GR-MD-02 increases the T-cell response to vaccination. Data was then obtained in several syngeneic tumor models in mice to evaluate the efficacy of anti-CTLA-4 and anti-PD1 monoclonal antibodies alone and in combination with GR-MD-02. As shown below, the addition of GR-MD-02 resulted in augmented tumor shrinkage in both prostate and breast cancer models.
These data were presented as part of the annual stockholder meeting on May 23, 2013 which can be viewed on the Galectin Therapeutics website (http://bit.ly/11QKp2P).
Notes to the reader:Checkpoint Blockade involves molecules on the cell surface of CD4 and CD8 T cells. These molecules serve as "brakes" to down-modulate or inhibit an anti-tumor immune response. Checkpoint Blockade Inhibitors release the "brakes" and thereby increases the immune response. Syngeneic tumor models in mice use mouse tumors in immunologically normal mice and therefore allow evaluation of the effect of the immune system on the tumors.
YERVOY" is a registered trademark of Bristol-Myers Squibb Company
Keywords for this news article include: Tumors, Oncology, Vaccination, Immunization, Blood Proteins, Cancer Vaccines, Serum Globulins, Pre-Trial Research, Monoclonal Antibodies, Galectin Therapeutics Inc., Clinical Trials and Studies.
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