Thursday, May 29, 2008

Steele Children's Research Center's Novel Cancer Vaccine

[Source Deb Daun, Bio5] - A novel therapeutic cancer vaccine developed by a research team at The University of Arizona Steele Children’s Research Center is advancing toward use in human clinical trials.

Dr. Emmanuel Katsanis, professor of pediatrics and a BIO5 member at the UA, and his research team developed the vaccine Chaperone Rich Cell Lysate, or CRCL, which utilizes proteins known as chaperone proteins. These special proteins are found inside cancer cells and are associated with the protein antigens unique to the individual’s cancer.

These antigens are needed for the immune system to identify the cancer to initiate an immune response to both destroy the existing tumor cells and boost the immune memory to protect against any recurrence of the tumor. However, in the individual with cancer, these tumor antigens are concealed from the immune system.

The CRCL vaccine employs a patented process that purifies the chaperone protein from the antigen, making the antigen again visible to the immune system. Previous therapeutic cancer vaccines have had disappointing results in the clinic, in part due to the difficulty in revealing these hidden tumor antigens; however, an additional problem is the sophisticated ability of tumor cells to avoid an immune response even when the tumor antigens have been revealed.

To overcome this tumor resistance, Katsanis has partnered with an Israeli biopharmaceutical company that has developed a cell therapy drug product called AlloStimTM – designed to provide the signals necessary to disable tumor immune avoidance mechanisms.

“We’re excited to see our research progress from the laboratory and move to human clinical trials, the combination of our technology to reveal hidden tumor antigens and the technology of Immunovative Therapies to disarm the tumor’s ability to avoid the immune response creates a powerful and unique combination that holds promise to overcome the past failures of cancer vaccines in the clinic,” Katsanis said.I

mmunovative Therapies, LTD, a cancer research-and-development company based in Israel, purchased an exclusive license to the chaperone protein patent held by the UA’s Steele Center. Immunovative Therapies is converting Katsanis’ chaperone protein technology to comply with Good Manufacturing Practices, required before beginning human clinical trials.

The new vaccine product, which combines CRCL and AlloStimTM, is named AlloVax and is designed to treat patients with newly diagnosed blood cancers like leukemia, lymphoma and multiple myeloma. When an individual develops a blood cancer, aggressive chemotherapy often can induce remission; unfortunately, because these treatments are unable to eliminate all of the microscopic cancer cells, the cancer frequently returns.

The returning cancers are deadly because they have developed a resistance to chemotherapy. AlloVax is designed to train the cancer patient’s immune system to identify and eliminate the cancer cells in the patient’s blood, keeping the patient in remission without the need for additional treatment.

Before an individual diagnosed with a blood cancer is treated with chemotherapy, a sample of the cancer is removed from his or her body. While receiving chemotherapy, the cancer sample is processed in the lab to extract the chaperone proteins.

Utilizing the UA’s patented process of purifying the chaperone proteins associated with the patient’s unique cancer antigens, the chaperone proteins then are mixed with Immunovative Therapies AlloStim cells. The mixture is injected into the patient’s skin.

Within the skin are specialized immune cells called dendritic cells, which then travel to the injection site and surround the chaperone proteins and unique cancer antigens that previously were hidden by the cancer cells. In the presence of danger signals released by AlloStim cells, these dendritic cells process the cancer antigens and are programmed by the AlloStim cells to understand that the cancer is a danger to the body.

The programmed dendritic cells containing the unique cancer antigens travel to the lymph node, where these programmed dendritic cells educate the patient’s T cells to destroy the cancer cells. These “educated killer T cells” will circulate in the body and continuously look for any cancer cells that might emerge. In the event of cancer recurrence, the T cells will destroy the cancer cells.

“AlloVax is truly a personalized and novel vaccine designed to train the immune system to destroy cancer cells,” Katsanis said. “It is designed to keep you in remission after you have been treated with chemotherapy and/or radiation. And now we are one step closer to treating patients with cancer.”

An animation of the process is available at:

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