Completing an important step in the evaluation of a cancer vaccine that has the potential to selectively target a wide range of tumors, researchers at the Ludwig Institute for Cancer Research report that the NY-ESO-1 ISCOM(r) vaccine (the Vaccine) safely activated a specific immune response in most cancer patients. The results, which are to be presented at the American Society of Clinical Oncology Annual Meeting in Orlando, demonstrate for the first time that a NY-ESO-1 full length protein can stimulate anti-cancer defenses.
"There are a number of vaccine strategies that might work against cancer, but NY-ESO-1 proteins are particularly exciting because they can possibly help a wide range of patients," said the study's lead author, Dr. Jonathan Cebon, of the Ludwig Institute for Cancer Research, Melbourne Branch. "The Vaccine showed a clear cause and effect in eliciting both NY-ESO-1 specific antibody and cellular-mediated responses."
To attack cancer, immune cells must recognize protein molecules known as antigens located on the surface of tumors. NY-ESO-1, a Cancer/Testis (CT) antigen, is one of the most recognizable tumor antigens discovered so far. In a previously published study, almost half of all patients with advanced NY-ESO-1 tumors and evidence of cancer showed natural immunity to the antigen. Because CT antigens are found only in tumors and a few normal cells such as those in the testis, vaccines that stimulate an immune response to CT antigens should have little risk of harming healthy tissue, as has been demonstrated in the current study and others.
Researchers combined NY-ESO-1 protein with the ISCOM(r) (ImmunoStimulating COMplex) adjuvant, which has been developed by CSL Limited of Melbourne, Australia. The ISCOM(r) adjuvant is comprised of saponin, cholesterol and phospholipid and is a potent stimulator of the immune system. A total of 46 patients (most had melanoma tumors that were NY-ESO-1 positive) with minimal or no residual disease after surgery received either the Vaccine (n=26) or NY-ESO-1 protein alone (n=20) for three months. Four patients in each group were given a placebo.
The majority of patients who received the Vaccine developed specific immunological responses, evaluated by sophisticated laboratory tests for NY-ESO-1 specific antibody, delayed type hypersensitivity (DTH) and CD8+ T-cells. In contrast, patients who received the Vaccine at lower doses or NY-ESO-1 protein alone had significantly lower immune responses.
The vaccine was well tolerated, with minor flu-like symptoms, fever, and malaise being the most common side effects. Pain at injection sites required a reduction in the doses given to three patients.
"This is an important first step for the Vaccine, which has great potential for treating a wide-variety of cancers," said Dr. Cebon. "We can now go on to see if the immune response from the vaccine is enough to attack tumors"
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