An Israeli biopharmaceutical start-up is developing a treatment for cancer patients designed to harness the power of the patient's immune system in order to destroy cancer cells in the body.
The potentially revolutionary immunotherapy drug, developed by Shoham-based company Immunovative Therapies, incorporates living immune cells as the active ingredient in the treatment, stimulating the body's own immune system to fight the tumor. The drug, AlloStim, has already been successfully tested in animal trials, and Phase I/II clinical trials on patients with advanced blood cancer will begin at the end of this year, or the start of 2008.
Cancer is a growing problem worldwide. Over recent decades, the incidence of cancer has escalated dramatically, now striking nearly one in two men, and more than one in three women. In the US alone, 1.2 million people are diagnosed with cancer every year, and half of them die as a result of the disease. The National Cancer Institute estimates that the number of cancer cases will increase further as the population ages.
"The battle against cancer is a battle we are losing," admits Michael Har-Noy, founder and CEO of Immunovative Therapies. But he hopes to be part of the change in the battle techniques being employed by doctors.
Despite dramatic advances in medicine, conventional cancer therapies - surgery, radiation and chemotherapy - remain much the same today as they have for decades. All three are drastic treatments, and both radiation and chemotherapy affect normal cells causing severe side effects. The major limitation of these therapies is their inability to eliminate the last tumor cell. Any remaining cells proliferate and cause a relapse. These new cells are often resistant to chemotherapy/radiation treatments, leaving the patient with what can be an untreatable disease.
Immunotherapy is a new form of treatment that researchers have been investigating for the last two decades. It uses the human immune system to seek out and destroy cancer cells wherever they reside in the body. Initially this field of medicine was considered one of the most promising potential treatments for cancer because it seemed to offer up the hope of getting rid of every single tumor cell. Animal trials went well, but when the new treatments reached human trials they inevitably failed.
"The problem was that it was easier to train a mouse's immune system to fight a tumor, than to train the human immune system," Har-Noy told ISRAEL21c. "Tumors in humans seem to have evolved a very sophisticated mechanism to avoid an immune attack."
With this in mind Har-Noy, who had been working in the field of immunotherapy in California for over 20 years, decided to try an alternative approach. He began researching bone marrow transplants (BMT), the one area of medicine where it has been proven that the immune system can cure patients of cancer.
With BMT, which is used to treat blood cancer, immune T-cells from a tissue-matched donor are transplanted into the patient. These transplanted immune cells kill the tumor cells, overcoming the tumor's immunoavoidance mechanisms, in what is known as the 'graft vs. tumor' effect. The result is the complete eradication of cancer, even in cases where patients had large tumors that were unresponsive to other cancer treatments.
While this can cure the patient, in 50% of cases, the new immune cells cause a serious and sometimes fatal side effect known as graft vs. host disease (GVHD), when the transplanted immune cells recognize both normal and tumor cells as foreign and mount attacks against both indiscriminately.
Har-Noy began looking for a treatment that would create the same anti-tumor effect of the BMT, without any of the toxic side effects. After three years of development, this is exactly what Immunovative believes it has achieved.
The company's new treatment, which can be used for virtually any type of cancer, works in two ways, firstly - like BMT - it disables the ability of the tumor to fight the immune response, and secondly it trains the patient's immune system to kill the cancer cells wherever it finds them.
The company takes T-cells from a normal donor and produces them ex-vivo in a nine-day proprietary culture process in a bioreactor. There is no need to match the donor to the recipient as required in BMT procedures. The AlloStim product is an intentional mismatch to the recipient. In the bioreactor the cells are activated with monoclonal antibody-coated particles that are removed before they are given to the patient.
"We provoke these cells, so that they become very 'angry' immune cells that are highly stimulated," explains Har-Noy. "Then we infuse them into the patient. The patient's immune system sees these new 'angry' cells as a great danger to the body, and rallies to the defense to eliminate the threat, releasing an array of inflammatory cytokines, in what is a bit like the fight or flight response of adrenaline."
These inflammatory cytokines, which remain in the body for between 24-36 hours, shut down the ability of the tumor to avoid an immune attack and at the same time enable immune-mediated killing of tumors spread throughout the body.
In the wake of this treatment, even if cancer cells recur in the body, the immune system can destroy them and does so automatically in much the same way that vaccines work. If a patient is treated for breast cancer, for example, and breast cancer cells begin to grow again after a few years, the immune system destroys them immediately. If the patient develops an alternative type of cancer, such as lung cancer, however, the AlloStim treatment will have to be repeated for that new type of cancer.
Patients who undergo the AlloStim treatment are not expected to suffer any side effects due to what the company calls the 'Mirror Effect'. The T-cells infused into a patient do not attack the patient's immune system, but stimulate it to attack the tumor. This is known as the host vs tumor (HVT) effect, and is the mirror image of the GVT effect. Unlike the GVH effect, it is not toxic, representing a new concept in the treatment of cancer.
"We'll know for sure when we treat patients, but we aren't anticipating any kind of toxic response," says Har-Noy.
The three-year-old company, which works from labs at Hadassah-Hebrew University Medical Center and Tel-Aviv Sourasky Medical Center, has already carried out successful animal trials on mice. "We were able to show that we could cure many types of tumors located throughout the bodies of the mice. A high percentage of the mice were cured without the GVHD side effect," says Har-Noy.
While animal trials were also successful in immunotherapy treatments that later proved unsuccessful in humans, Har-Noy believes this is different. "We reverse engineered a new response that works in humans and just tested the principle on mice," he explains.
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