Next-Generation CAR-T Cells Targeting Melanoma
Abstract
GD2 gangliosides are a special type of sugar containing fat molecules that are over-expressed on several solid tumors, including melanoma, but show restricted expression on normal healthy tissues. Chimeric antigen receptor T (CAR-T) is a novel approach to genetically engineer immune cells to kill cancer cells. Despite the success of CAR-T in blood cancers, there are several limitations to this approach, including lack of efficacy against solid tumor and toxicities. To overcome the above design limitations of the current generation CARs, we have developed a next generation platform, designated synthetic immune receptor (SIR). The main objective of the proposal is to generate a panel of SIR-T cells targeting GD2 gangliosides for the treatment of melanoma and to demonstrate their efficacy and safety using pre-clinical studies. At the end of the project period, we hope to have demonstrated the safety and efficacy of GD2 SIRs that will lay the foundation for IND-enabling studies for initiation of human clinical trials. In the long term, the GD2 SIR-T cells developed by this project could potentially revolutionize the treatment of melanoma as a single injection of GD2 SIR-T cells could potentially result in long-term remission and perhaps cure of even advance metastatic disease. The GD2 SIR-T of the current proposals could be also combined with other forms of immunotherapy and/or targeted therapies to further improve the response rate or duration of remission. The project is highly relevant to military health, as there is an increased risk of melanoma among the military personnel with the incidence rates of melanoma approximately 60% higher than in general population.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210965
Entities
People
- Preet Chaudhary
Organizations
- United States Army
- University of Southern California