Testing Different Vaccine Approaches to Defeat Cancer

As part of a far-reaching effort to develop effective anti-cancer vaccines, investigators at the Ludwig Institute for Cancer Research announced four separate findings related to a natural cancer opponent known as NY-ESO-1. In one study, a Ludwig team found that immune cells can respond on their own to advanced tumors that express NY-ESO-1 antigens, possibly keeping the disease at bay.

By stimulating these cells further with an antigen-based vaccine, researchers hope to unleash an immune response that is powerful enough to control cancer. Three other Ludwig teams took preliminary steps to prove just that, with studies showing how different strategies may boost immune responses to NY-ESO-1.

"We are taking a broad approach to developing a possible cancer treatment, rather than just focusing on one strategy," said Dr. Eric Hoffman, Director of Clinical Trials Management at the Ludwig Institute. "This will not only help us determine if NY-ESO-1 truly works, but it can also teach us important lessons on how to best stimulate an immune response against cancer."

NY-ESO-1 is a particularly interesting vaccine target because it is found almost exclusively on cancer cells and the antigen provokes a spontaneous immune response in a surprisingly high number of patients. A study led by Dr. Padmanee Sharma of the Ludwig Institute's New York Branch at Memorial Sloan-Kettering helps define who could potentially benefit from this type of therapy.

Analyzing various tumor specimens, Dr. Sharma's team found that NY-ESO-1 was commonly expressed in advanced bladder cancers. Out of 43 high-grade bladder tumors that had been recently collected, for example, more than 50% were positive for NY-ESO-1. Most remarkably, the team discovered that one person with a NY-ESO-1 positive tumor showed a major immune reaction directed against the antigen. The patient, who had a bladder tumor surgically removed, was still free of the disease 18 months later.

"We can't say for sure if having an immune response to NY-ESO-1 helped this patient, but it's clearly a positive sign that immune cells reacted to the tumor," said Dr. Sharma, who received the ASCO Young Investigators Award to further support her research. She plans to investigate how bladder cancer patients respond to a NY-ESO-1 vaccine.

Previous studies have shown that NY-ESO-1 vaccines can stimulate potential anti-cancer defenses in some patients. Dr. Elke Jaeger and colleagues attempted to improve upon these findings by using a special viral delivery system, as well as a more intense vaccination schedule.

In one study presented at ASCO, Dr. Jaeger's team found that adding a disarmed fowl pox virus to the vaccine elicited a specific NY-ESO-1 immune response in seven patients who had either melanoma, sarcoma, or ovarian cancer. Another study presented at the meeting found that injecting patients with NY-ESO-1 once a day for nearly a week promoted earlier and bigger immune responses than what is typically seen with more prolonged vaccinations.

"We are continuing to search for the best way to use NY-ESO-1," said Dr. Jaeger, a Ludwig affiliate at the Krankenhaus Nordwest medical facility in Frankfurt, Germany.

Ludwig investigators and outside colleagues also sought to increase the odds by stimulating the immune system before possible vaccination. According to results presented at ASCO, the researchers found that injecting melanoma patients with a special growth factor and then adding a prescription cream called Aldera (imiquimod) to the skin could prime the immune system to specifically attack the NY-ESO-1 antigen.

Though the effects were modest, study author Dr. Jonathan Cebon of the Ludwig Branch in Melbourne, Australia, said that the use of so-called toll-like receptor ligands might be enhanced with further research.

The Ludwig Institute continues to pursue NY-ESO-1 in clinical trials, including a major collaboration with six leading medical institutions in New York City, where NY-ESO-1 was discovered. Unique for this type of collaboration, researchers will test NY-ESO-1 vaccines in a similar fashion so that different strategies can be equally compared.

"We want to develop an effective vaccine as quickly as possible without short cutting the detailed science that is needed," said Dr. Hoffman. "Hopefully, we can find the type of answers that may lead to an effective and less toxic treatment for cancer."

The Ludwig Institute for Cancer Research is a not-for-profit global research organization that addresses the complex nature of cancer through a range of scientific disciplines, including genetics, tumor immunology, and cell biology and signaling. Convinced that the discovery process has not run its course until promising laboratory findings are tested in the clinic, the Institute is an active sponsor of its own clinical trials.