Dendritic cells (DC) are specialized immune cells that help develop immune responses (B and T cells) against pathogens/microbes and cancer. DCs can be used as therapy. DCs can be taken out of the body, modified to recognize cancer cells, and once re-injected, can improve immune responses (B and T cells) against cancer. Small clinical trials have demonstrated that DC vaccines are safe and can lead to improved immune responses against cancer, however, the two large clinical trials had mixed results. This is probably because there is not enough known about how to make the best DCs that will be most effective against cancer. Our own clinical trial that compares DCs with a widely-used vaccine adjuvant showed that the vaccine adjuvant was better in stimulating immune responses against melanoma, a type of skin cancer. A promising new strategy to help DCs is by activating specialized proteins found on DCs called Toll-like receptors (TLR). TLRs are a type of pattern recognition receptor (PRR) and recognize molecules that are broadly shared by pathogens/microbes, referred to as pathogen-associated molecular patterns (PAMPs). Activation of TLRs on DC leads to enhancement of the ability of DCs to stimulate effective immune responses. Our own studies showed that activation of TLRs stimulate immune responses in patients with melanoma. We believe that activating these TLRs on DCs will be an important step in generating the best DCs to stimulate immune responses against melanoma that is effective. We propose several projects with the goal of improving DC vaccines that stimulate effective immune responses against cancer. In Project 1, we will study the effects of activating TLRs using animals that have melanoma. Our lab showed that DCs and other immune cells inside the body would need to cooperate with the DC vaccine in order to activate immune responses. We will activate TLRs on the DC vaccines as well as TLRs on other immune cells inside the body to see its effects on the cancer cells inside the animals. There are different TLRs found on DCs and activation of each leads to different effects. As part of Project 2, we will evaluate the effects of activating the different TLRs on DCs and also use different antibodies, known to enhance DC function, to see if we can improve immune responses. Finally, in Project 3, we propose a clinical trial based on knowledge we have gained from our studies in Projects 1 and 2. Patients in the clinical trial will receive a DC vaccine injection that is activated using TLRs followed by another injection of proteins that activates TLRs on DCs and other immune cells in the body. We will look to see if we can enhance immune responses in patients with melanoma. We will work with researchers and clinicians at NYU Langone Medical Center, Memorial Sloan Kettering Cancer Center, and the Ludwig Institute of Cancer Research to meet the ultimate goal of improving DC vaccines.
|Effective start/end date||1/01/10 → …|
- Melanoma Research Alliance
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