Tuesday, February 21, 2012

Targovax Vaccine against Pancreatic Cancer

Targovax, an oncology biopharma company,  announced February 1, 2012 that it has secured NOK 13 million (USD 2.2 million) from a consortium comprising the Radium Hospital Research Foundation, Birk Venture, RO Invest and existing owners for further development of its lead candidate, TG01, a therapeutic vaccine for pancreatic cancer. This funding follows the award of an Innovation Norway grant of NOK 9 million in early December 2011.

Hanne Mette D. Kristensen, CEO, states “We are delighted to have secured significant private and public funding for the project. This will enable us to file an application and manufacture first GMP batches for clinical trials. We aim to recruit the first patients in clinical studies by the end of Q4, 2012.”

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For the last 20 years, Gustav Gaudernack, the Emeritus Professor at the Institute of Cancer Research at the University of Oslo, Norway, has researched into various vaccines against pancreatic cancer. This is one of the cancers with the highest mortality rate and lowest survival rate. The average life-time after surgery is only 18 months.

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Gaudernack's research team tested the first tailored treatment against pancreatic cancer in 1993. A specific gene in the cancer cells had mutated in 9 out of 10 patients. There were seven different mutations. Therefore, Gaudernack produced a cancer vaccine that was to stimulate the immune system to attack those cancer cells containing these mutations. Last year saw the study on long-term survival, in which 130 patients were followed over 10 years. All had undergone surgery. 23 received the cancer vaccine. A fifth of the vaccinated patients survived seven to ten years. None of the non-vaccinated patients survived for any length of time.

“These figures are highly reliable. On average, patients receiving the vaccine survived twice as long as those who had not been vaccinated,” comments Gaudernack to the research magazine Apollon at University of Oslo. Only 15% of patients can be operated for pancreatic cancer. If it is not possible to operate, the average life-time is less than six months.

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In 2000, Gaudernack had a new vaccine ready for those patients who could not undergo surgery. "Treatment options for this group of patients have practically been at a standstill for the past 30 years, in spite of a new form of chemotherapy that has increased the life-time by a few months.”

The British Cancer Society has now tested this cancer vaccine on 1100 patients at 50 English hospitals. The patients were allocated to three groups. One group only received chemotherapy. The second group received either chemotherapy or the cancer vaccine. The third group received chemotherapy and the cancer vaccine at the same time.

The results are now being analyzed by an independent group and will be published in the autumn of 2011. Gaudernack has so far not been informed, but his expectations are high. “If the results had been clearly negative, the study would have been stopped early. If the results are positive, the cancer vaccine will be commercialized. It will also be possible to use the vaccine on other types of cancer such as lung cancer.”

Now Gaudernack’s research group is working on in an entirely new cancer vaccine that is intended to prolong the lives of patients with other types of serious, highly advanced cancer. The new vaccine is comprised of three components which the immune system of long-term survivors will react to.

 “In the first part of the study we will investigate possible side effects and determine the optimum dose. We can only do this by measuring the immune response. An indicator of whether the vaccine is working is that the immune response is greater in those who survive longer than those who do not survive for very long. However, this is not enough to get the vaccine approved. Just as with all medical developments, the vaccine must also be tested in studies in which the patients are randomly given either the vaccine or standard of care treatment.”

The vaccine ensures that the immune system kills all cells that divide infinitely. Most cancer cells divide infinitely. This is due to the enzyme telomerase. Healthy cells can only divide a limited number of times. This is to do with the way the chromosomes are structured. A chromosome contains all the gene material in a cell. Telomeres are regions at the tips of the chromosome that contain repeating sections. Each time the cell divides, one piece falls off. This causes the cell to age. When the cell has divided many times and there are no more sections left, the cell dies.

“You can compare this with a “pay-as-you-go” card. Healthy cells can only divide a certain number of times. Therefore it is important that you are born with as many units as possible. If the cancer cells divided only a limited number of times like the healthy cells it would be easier to fight cancer. But unfortunately, the enzyme telomerase makes sure that the telomere bit is always re-attached to the chromosome so that the length of the chromosome remains constant. This means that cancer cells have an unlimited “pay-as-you-go card” with an infinite number of units. Cancer cells can therefore divide an unlimited number of times.” The vaccine destroys this possibility.

This special enzyme is also found in stem cells and sex cells. However, the vaccine does not kill the stem cells. Researchers still do not know why. This special telomerase enzyme is found in nine out of ten cancer cells. Gaudernack hopes therefore that the vaccine can be used against all types of cancer. “In far-advanced cancer, where other treatment is unsuccessful, we hope to delay the development of the disease. If there is a danger of recurrence we hope to be able to delay or prevent this recurrence. And if the cancer is discovered early we hope that the vaccine will enable complete recovery,” states Gustav Gaudernack.

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About TG01 Vaccine

The lead Targovax product, TG01, is a peptide vaccine that targets mutations in the ras genes that are associated with cancer. Mutation of ras disrupts normal cell division signalling and contributes to development of cancer cells and tumours. Ras mutations are found in approximately 25% of all cancers and in particular in pancreatic cancer (80-90%), colorectal cancer (40%) and non-small cell lung cancers (30%).

Currently available cancer treatments have very little or no effect on cancers with ras mutations.

Targovax is preparing to initiate a phase II clinical study with TG01 for adjuvant treatment of patients with pancreatic cancers that have undergone surgery. As of today, the only potentially curative treatment for pancreatic cancer is surgery, primarily in cases where the disease is diagnosed in the early stages. However, the risk of relapse of the disease after surgery is very high and only 15% of the patients undergoing surgery are still alive after 5 years

The T cells of the patient's immune system are stimulated to attack cancer cells. Following intradermal administration, the vaccine peptides are taken up by antigen presenting cells that migrate to the lymph nodes and present the peptides to T cells. Subsequently the T cells get activated and enter the body's circulation with a potential to kill, or to stimulate the killing of, cancer cells.

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