Testicular protein vaccine may fight ovarian cancer

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Testicular protein vaccine may fight ovarian cancer
22:00 23 July 2007
by Roxanne Khamsi
NewScientist

Could a protein found in the male testes protect women against a recurrence of ovarian cancer? That is the hope of scientists based on the results of an early stage clinical trial testing a therapeutic vaccine against the illness.

Preliminary results from the study suggest that the vaccine has the potential to stimulate the body's immune system in a way that might delay the recurrence of ovarian tumours.

The vaccine used in the trial relied upon fragments of a protein known as NY-ESO-1. Although both men and women carry the genes for this protein, it is normally only produced in the male testes. But, for unknown reasons, the gene gets switched on in 40% of ovarian tumours.

Kunle Odunsi at the Roswell Park Cancer Institute in Buffalo, New York, US and his colleagues recruited 18 women who had experienced multiple recurrences of NY-ESO-1-positive ovarian cancer for a phase I clinical trial to test a vaccine based on the protein.

Recognise and destroy
At the start of the study, none of the subjects had any ovarian tumours, but they were at high risk of redeveloping them.

Odunsi's team hoped their vaccine would stave off a further return of the cancer in such patients by training the immune system to recognise and destroy NY-ESO-1 positive cells. They gave the women up to five injections of the protein over a four-month period.

The median survival time of women enrolled in the study was less than two years. But of the 18 participants, 15 (83%) of them showed a positive immune response to the vaccine. Typically, ovarian cancer patients do not have detectable levels of "CD4" immune cells that specifically target NY-ESO-1-positive tissues. But among the subjects who responded to the vaccine, as much as 1% of the CD4 cells circulating in their bodies reacted to the protein.

These women did not experience a recurrence of ovarian cancer for a year, on average, according to Odunsi. By comparison, the three women who showed no immune response following vaccination saw their cancer return within an average of six months.

'Significant response'
"As a proof of principle it's a very interesting study," says Carmel Cohen, chairman of the board of the Ovarian Cancer Research Fund in New York. "This might be a very good platform for going forward in this direction."

Odunsi acknowledges it is impossible to draw conclusions about the power of the vaccine to delay recurrence based on the small study. But he says the significant immune response seen in the patients makes him hopeful that the phase II trial, already in progress, will also show a benefit from the vaccine.

He adds that the phase II trial involves the use of the whole NY-ESO-1 protein, rather than only a fragment of it, and attaching it to a harmless virus - measures which should both induce an even larger immune response.

In the phase I trials, Odunsi has seen "pretty much no side effects besides pain and rash at the injection site". He notes that the vaccine uses a human protein, and is therefore perhaps riskier than a vaccine against a virus, because it might prompt an autoimmune reaction. He says however, that the likelihood of this happening is "incredibly small".

Preventative hope
Odunsi stresses "it is a therapeutic vaccine to prevent relapse" of ovarian cancer. But he says one day, if it proves safe and effective, it could possibly be used as a prophylactic treatment for women who carry BRCA gene mutations and therefore face a high risk of developing ovarian tumours.

"One can envision that you could vaccinate as a preventative measure" in this group of women, he says.

Experts, though, caution that the prospect for tackling ovarian cancer this way remains distant: "We are far from developing an effective ovarian cancer vaccine," says Judith Wolf, chair of the US National Ovarian Cancer Coalition's medical advisory board. "There are several investigators around the country who are working on this, but only a few vaccines have made it to clinical trials in patients."

Other approaches to developing a therapeutic ovarian cancer vaccine have involved using cells from the patients' own tumours to stimulate an immune response.

Each year, an estimated 25,000 women are diagnosed with ovarian cancer in the US alone. Recent studies have suggested that hormone replacement therapy to treat, for example, symptoms of menopause, might increase the risk of dying from this type of cancer.

Journal reference: Proceedings of the National Academy of Science (DOI: 10.1073_pnas.0703342104)

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