Ludwig Institute for Cancer Research

New York (September 30)—The Cancer Research Institute and the Ludwig Institute for Cancer Research (LICR) announce the launch of the Cancer Vaccine Collaborative (CVC), a unique research program that should dramatically improve how cancer vaccines are developed.

What is the Cancer Vaccine Collaborative (CVC)?

The CVC is an innovative clinical research program designed and directed by the Cancer Research Institute and the Ludwig Institute for Cancer Research. The collaboration involves an unprecedented network of clinical investigators from six local New York medical centers all working together to conduct a series of early-stage clinical trials on cancer vaccines. The goal of these trials is to teach us how to effectively immunize against cancer.

Why New York?

New York is home to some of the leading medical research centers in the country, and many of the discoveries that have brought us to this point in cancer research were made in New York. Initiating the CVC in New York allows us to bring together clinical investigators in our area who can share their expertise for one specific purpose. As the CVC matures, we plan to expand its reach to include medical centers in other major metropolitan areas.

Why now?

The science of cancer immunology has progressed far enough that vaccine strategies warrant deeper investigation. Foremost among these discoveries are:

How is the CVC different from typical clinical trial approaches?

Unlike conventional, stand-alone trials—where data from one trial are often incomparable to data from another because of the number of uncontrolled variables between the two—investigators for the CVC will use standardized tests to evaluate different ways to deliver the same vaccine agent, the antigen NY-ESO-1. This standardized methodology and data collection will allow for direct comparison with other trials in the CVC and help the researchers understand why certain vaccine strategies might result in a more robust immune response while others might not. Moreover, the studies will be coordinated and done in parallel with each other rather than sequentially, potentially speeding up the time promising discoveries can end up helping patients. And since the CVC is an academic-based enterprise rather than a product-driven one, investigators can systemically evaluate each vaccine strategy from a more objective perspective. The key benefit of such a research model is that we stand to learn much about the correct delivery of immunizing agents even if clinical responses aren’t seen.

What is NY-ESO-1, and why are you focusing the CVC trials on it?

The cancer antigen NY-ESO-1 is made by many different types of human tumors. The protein was discovered in an esophageal tumor in 1997 by a team of scientists at the Ludwig Branch in New York and Weill Cornell Medical Center. Subsequently, NY-ESO-1 was found in a proportion of a broad range of solid tumors, including melanomas, sarcomas, and tumors of the breast, ovary, and lung. Antigens are what the immune systems relies on to identify potential threats, and NY-ESO-1 is one of most highly immunogenic tumor antigens discovered so far. In other words, many advanced cancer patients whose tumors synthesize this protein develop immune reactions to it. NY-ESO-1 appears to elicit both cellular and humoral immune responses, a combination that may be best suited to attack tumors. Such traits make the NY-ESO-1, or peptides derived from it, potentially useful vaccine components for treating a sizeable percentage of cancer victims. Therefore, NY-ESO-1 has become a model antigen for cancer vaccine researchers and one that the CVC will focus on initially.

Who is participating in the CVC?

Currently, investigators from six medical centers and hospitals are participating, including:

How were these investigators selected for participation?

A committee of scientists and clinicians from CRI and LICR select the institutions and investigators to participate in the Cancer Vaccine Collaborative and then work closely with them to design Phase 1 and 2 clinical trials. Many of these clinicians have a desire to develop cancer vaccines but lack the capability of producing the antigens, meeting the clinical trial requirements, and monitoring specific immune responses. The CVC takes care of all of these aspects of running trials, making it much more feasible for the investigators at these institutions to participate.

How many trials are running now?

Currently, ten trials are either active or in preparation to activate. Targeted cancers include non-small cell lung cancer (at Cornell), melanoma (at Columbia-Presbyterian and New York University), ovarian cancer (at Roswell Park and Memorial Sloan-Kettering), prostate cancer (at Mount Sinai), bladder cancer (at Memorial Sloan-Kettering), sarcomas (at Memorial Sloan-Kettering and Columbia-Presbyterian), and a trial at Columbia-Presbyterian for cancers that express either the NY-ESO-1 or related LAGE antigens.

How are patients selected to participate in these trials?

As in all clinical trials, patients must meet eligibility requirements to participate in the CVC trials. For most of these vaccine trials, patient cancers must express the NY-ESO-1 antigen, which can be determined through testing. For eligibility questions specific to each trial, interested individuals can contact the Cancer Research Institute for more information.

Who funds these trials?

The Cancer Research Institute supplies grant monies to the participating institution’s to cover much of the cost associated with the clinical delivery of vaccine therapies. These funds are significantly leveraged by the Ludwig Institute’s contribution of reagents, lab follow-up, and data monitoring.

What strategies are being used to modify the immune system to fight cancer?

Researchers from around the world are currently testing four broad types of cancer immunotherapies. One approach is “non-specific immunotherapy,” so named because the strategy strengthens the overall activity of the immune system instead of selectively arousing those elements most able to combat cancer. They have the longest history and are based on observations that tumor regressions can occur in patients experiencing bacterial infection. Microbial products such as Bacilli Chalmette-Guerin (BCG), as well as interferons, interleukins, and tumor necrosis factor (TNF) are all non-specific forms of immunotherapy.

“Passive immunotherapy” entails the use of antibodies.Circulating in the blood, antibodies seek out and bind to antigens found on the surface of foreign cells, marking them for destruction. Antibodies that target the CD20 antigen on lymphoma (Rituxan) and the HER/2-neu antigen in breast cancer (Herceptin) have received FDA approval as cancer treatments.

“Adoptive immunotherapy” involves stimulating T cells by exposing them to tumor cells or antigens in the laboratory and then injecting expanded populations of the treated cells into patients. Re-injected cells can now survive for longer periods of time in patients and recent efforts have proven successful in treating a limited number of patients with advanced melanoma.

“Active cancer immunotherapy” refers to vaccines that rouse immune system components to vigorously attack malignant tissue. There are numerous sub-categories of these cancer vaccines, including whole cancer cells (inactivated cancer cells and their extracts that jump-start the immune system), peptides (fragments of tumor proteins recognized by T cells), and proteins(antigen-presenting cells that take up injected tumor proteins and break them down into fragments recognized by T cells). The CVC is testing active cancer vaccines that utilize different methods to deliver the NY-ESO-1 antigen.