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Identification of 'biological brake' could improve cancer vaccines

By Ruth SoRelle, MPH

Si-Yi Chen, MD, PhD

Worldwide, more than 1,000 people have received tumor vaccines to varying and often disappointing effects. Now a researcher at Baylor College of Medicine thinks he may have identified a biological brake that prevents the vaccines from marshalling the body's immune system effectively against the invading cancer.

Tumor vaccines attempt to alert the body to the presence of cancer by using dendritic cells that present proteins called antigens to the immune system. Tumor cells make too much antigen, which should be a red flag to the immune system. If it is, the immune system responds by activating immune cells that attack tumor cells expressing the self antigens.

"It's like driving a car," said Si-Yi Chen, MD, PhD, associate professor in the Center for Cell and Gene Therapy and department of molecular and human genetics of BCM. "Everyone tries to step on an accelerator, but that doesn't work well if the brake is on." A report of this work appears in a recent issue of the journal Nature Biotechnology.

Such vaccines depend on dendritic cells and their normal activities to motivate the immune system. Vaccines based on this principle have been developed against melanoma, kidney, breast, ovarian and colon cancers, among others.

The brake to which Chen referes is a protein in dendritic cells called suppressor of cytokine signaling (SOCS) 1. SOCS1 prevents the immune system from marshalling its forces against a cancer. In a normal system, SOCS1 is critical because it prevents overreaction on the part of the immune system.

"The brake is always there to avoid the autoimmune response," said Chen. Autoimmune diseases such as lupus, rheumatoid arthritis, scleroderma and type 1 diabetes arise because the immune system becomes confused. The immune system is usually able to differentiate between "self" and "non-self." "Self" means tissues, cells and protein produced within an individual organism. "Non-self" refers to bodies that are foreign and often inimical to the body.

"The brake is always there to avoid the autoimmune response," said Chen.

Chen and his colleagues found that tumor vaccines based on the use of dendritic cells were superior when SOCS1 was disabled. The new vaccines could incite an immune response to control tumor growth in mice.

"We are interested in moving this into clinical trials quickly," he said. "The true test is in humans."

Understanding SOCS1 better will also enable scientists such as Chen to understand better how the immune system works.

Others from BCM who participated in this research include: Dr. Lei Shen, Kevin Evel-Kabler, graduate student, and Dr. Randy Strube. Funding for the work came from the National Institutes of Health, the Leukemia and Lymphoma Society and the U.S. Army Prostate Cancer Research Program.

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