A new vaccine designed at The Rockefeller University boosted a type of fast-responding immune system cell called the natural killer T (NKT) cell in patients with advanced cancer. The study surprised researchers by revealing the ability of these NKT cells to spur other, slower-responding immune cells to go to work.
The findings are encouraging researchers at Rockefeller to pursue additional clinical research using the new NKT approach to improve T cell based vaccines against cancer and viral infections.
Results of this study are published in the May 2 issue of the Journal of Experimental Medicine.
The study began in July 2003 and treated 5 patients with advanced cancer who had no detectable NKT cells in their blood at the start of the study. The experimental vaccine led to considerable expansion of NKT cells in all patients that lasted for at least 3 months.
"This study clearly demonstrates the feasibility to specifically boost this important immune cell in humans and therefore opens the door for targeting the innate arm of the immune system against pathogens and cancer," says Madhav Dhodapkar, M.D., who led the study and heads the laboratory of Tumor Immunology and Immunotherapy at the university.
The duration of the expansion was also unexpected, says co-author Ralph Steinman, M.D., head of the Laboratory of Cellular Physiology and Immunology at Rockefeller, because most NKT cell responses are short-lived.
The power of NKT cells lies in their capacity to prompt many infection- and disease- fighting immune cells downstream of their initial, speedy response. This effect may be what's happening with the application of the new vaccine, according to the researchers.
The vaccine led to enhancement in what's known as adaptive immunity, the immune response that does not take place immediately, but is more fine-tuned to specific foreign invaders like microbes or mutated cells.
NKT cells are part of what's known scientifically as the innate immune response, or that part of the immune response that should, under normal circumstances, respond quickly. Most prior cancer vaccines have focused on the adaptive immune system. What's more, prior attempts to mobilize NKT cells in humans have met with limited success.
"Early events of the immune system may determine what happens down the line," says Dhodapkar. "In cancer, we've learned that both arms of the immune system are defective." The absence of a coordinated immune response may allow cancer cells to grow and spread.
Using mature dendritic cells might be one of the keys to attaining consistent results, says co- Steinman, a senior Rockefeller University scientist who discovered the dendritic cell in 1973. "The interaction of mature dendritic cells with NKT cells results in the production of many immune-enhancing cytokines," he says. Cytokines are molecular messengers produced by white blood cells, including dendritic cells, and they are an important part of the immune system's complex communications system. When scientists elsewhere carried out an experiment similar to the current study, but used immature dendritic cells, results were limited and not consistent.
Naturally occurring mature dendritic cells are known to do two things: one is to process and present antigen, or material considered foreign to the body. This presentation allows other immune system cells to recognize foreign material, which includes tumor cells. The other activity of the mature dendritic cell is to deliver "accessory" signals to immune system cells so that they expand or differentiate, or develop into, helpers or killers focused on removing an antigen. Cytokines are examples of these accessory signals. Mature dendritic cells used in the experimental vaccine may possess the correct chemical vocabulary with which to speak.
The Rockefeller researchers now are planning another clinical study in a larger population of cancer patients using their new strategy.