CryoVax(R) : Next Generation Immunotherapy for Metastatic Colorectal Cancer Begins USA Phase IIb Clinical Trial

JERUSALEM, Israel, Nov. 7, 2016 /PRNewswire/ -- Immunovative Therapies, Ltd., on behalf of it's subsidiary, ImmunoCare, Ltd., today announced the start of a Phase IIb study of CryoVax^®, a next generation immunotherapy cancer vaccine product, for patients with chemotherapy-refractory (third line) metastatic colorectal cancer (mCRC). The trial is being conducted by Banner MD Anderson Medical Center, in Phoenix, AZ, which is partnered with the world renowned University of Texas MD Anderson Cancer Center in Houston, TX, Recruitment in the trial is underway, and the first volunteers have received their initial vaccine doses. Enrollment is expected to be completed by the end of July 2017.

About 134,490 people are estimated to be diagnosed with colorectal cancer in the United States each year and about 49,190 of these patients die from the disease. The prognosis for patients with mCRC disease is extremely poor. Intensive research is being conducted to develop treatments for mCRC patients that become refractory to chemotherapy. There have recently been approvals of new agents for chemotherapy-refractory mCRC, but the efficacy of these new agents are modest and often accompanied by some rather significant side-effects. Accordingly, there is still an urgent need for new, effective and low toxic therapies for chemotherapy-refractory mCRC.

The success of checkpoint inhibitors in a subset of melanoma and lung cancer patients has elicited much excitement about immunotherapy as a new treatment method for cancer. However, checkpoint inhibition immunotherapy agents have not demonstrated promise in the treatment of mCRC.

Checkpoint inhibition seems to only be effective in mCRC in the rare occasion when patients present with highly mutated tumors, Highly mutated tumors attract an immune response resulting in tumors becoming heavily infiltrated with immune cells (known as 'hot' tumors). Only approximately 15% of mCRC patients present with these 'hot' tumors. The infiltrating immune cells in these 'hot' tumors are suppressed from killing tumor cells due to the expression of checkpoint molecules. When immune cells encounter checkpoint molecules, they are turned off and suppressed from performing killing functions. Checkpoint blockade immunotherapy can prevent the interaction of checkpoint molecules with immune cells, permitting the immune cells to perform killing functions. This is the mechanism thought to be responsible for the effectiveness of checkpoint blockade in the small subset of mCRC patients with highly mutated, immunologically-active mCRC tumors.  

CryoVax^® is a next generation immunotherapy designed to provide immune-mediated tumor killing effects for the remaining 85% of mCRC patients that fail to respond to checkpoint inhibition immunotherapy. The CryoVax^® next generation immunotherapy regimen is designed to create "hot" tumors in these patients and then naturally block checkpoint molecule expression. Patients are first immunized against patented bioengineered immune cells called AlloStim^® which are derived from healthy, intentionally mis-matched, donor cells. A vaccine is then created within the body which customizes the immune response to the patient's own tumor.

Vaccines contain a source of tumor antigens and an adjuvant to modulate the immune response. The tumor antigens for the CryoVax^® vaccine are derived from the release of the inner contents of tumors (i.e., heat shock proteins) killed by extreme cold, a technique called "cryoablation". Intratumoral injection of AlloStim^® cells into the microenvironment of the cryoablation lesion containing dead tumor cells serves as an adjuvant. This creates an in-situ, personalized, anti-cancer vaccine. Subsequent IV infusions of the AlloStim^® cells cause the movement of immune cells from the circulation into the tumor lesions. This movement of immune cells is predicted to create 'hot' tumors. The highly inflammatory conditions created by the subsequent rejection of the mis-matched AlloStim^® cells serves to naturally down-regulate checkpoint molecules on tumor cells. This combination of hot tumors and down-regulation of checkpoint molecules is a formula known to enable immune-mediate tumor killing of mCRC tumors.  

Dr Michael Har-Noy, CEO of Immunovative Therapies, Ltd. and inventor of the CryoVax^® anti-tumor vaccine regimen stated: "anti-tumor vaccines have had difficulties in translating into effective therapies in the clinic and mCRC has been particularly resistant to immunotherapy. The CryoVax^® vaccine regimen has a unique mechanism of action and shows promise as a next generation immunotherapy. We will be studying various AlloStim^® dosing frequencies and closely monitoring the interaction of host immune cells with the tumor cells in each of the cohorts of this clinical trial. This information should serve to determine if this customized in-situ vaccine approach will benefit mCRC patients."

The volunteers in this study will be sequentially enrolled into six groups (A through F) that will receive different dosing frequency schedules of AlloStim^®. All subjects receive cryoablation of a selected tumor lesion followed by intratumoral injection of AlloStim^® to create a customized in-situ vaccine. Subjects are required to undergo multiple biopsy and CT scan procedures and provide multiple blood samples over time. These materials are analyzed sequentially in order to study how the interaction of the mCRC tumors with the immune system changes over time. 

Dr. Madappa Kundranda, MD, PhD, the Principle Investigator on this study stated:" there is a clear need for alternative treatment options for chemotherapy-refractory mCRC tumors. We feel very fortunate to be chosen as the first institution in the United States to have the opportunity to evaluate the novel CryoVax^® vaccine technology and to provide this clinical trial option to our patient population. Response to chemotherapy treatments relies upon evaluation of changes in tumor size, however often times it is difficult to evaluate response to immunotherapy using these techniques. Immune responses can result in swollen tumors that appear larger but actually contain decreased tumor burden, initial pseudo-progression followed by response sometimes even months later, or stable disease that translates to increased survival. The incorporation of sophisticated immunomonitoring exploratory end-points and longitudinal biopsies and CT scans taken simultaneously in the trial design provides an unprecedented opportunity to understand the immune mechanisms involved in mCRC and to learn how different frequencies of CryoVax^® vaccine administration affects these parameters. We are confident that this trial will significantly add to our knowledge regarding the interaction of the immune system with chemotherapy-resistant tumors."

About Immunovative Therapies, Ltd. and ImmunoCare, Ltd.

Immunovative Therapies, Ltd. (ITL) is an Israeli biopharmaceutical company specializing in the development, manufacture and testing of next generation of immunotherapy products. ImmunoCare, Ltd. is a subsidiary of ITL that has been granted the exclusive worldwide marketing rights to CryoVax^® in colorectal cancer. ITL was founded in May, 2004 with support from the Israel Office of the Chief Scientist and Hadassah-Hebrew University Medical Center. The Company has operations in Jerusalem, Phoenix, AZ USA and Thailand.

For further information contact: Dganit Cohen: [email protected]

Website: www.immunovative.com

Tel: +972 26506288  

SOURCE Immunovative Therapies Limited

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