Tumors can develop unique genetic mutations which are specific to an individual patient. Some of these mutations are immunogenic; giving rise to autologous T cells which are tumor-reactive. Once isolated and sequenced, these neoantigen-specific TCRs can form the basis of effective adoptive cell therapy cancer treatment regimens; however, current methods of isolation are inefficient. Moreover, the process is technically challenging due to TCR sequence diversity and the need to correctly pair the a and b chain of each receptor. Thus, there is an urgent need for more robust methods of identifying paired sequences of mutation-specific TCRs for cancer immunotherapy.
Researchers at the NCI have developed an efficient method for isolating the paired sequences of TCRs. Using single-cell methodology, next generation sequencing and custom bioinformatics software, the researchers can isolate full-length TCR α and β chain sequences from mutation-reactive T cells. These isolated sequences can facilitate adoptive cell therapy for cancer patients.
- Personalized immunotherapy to treat cancer patients
- Research tool to identify mutation-specific T-cell receptors
- Broadly applicable to different types of malignant tumors
- Limited off-target effects
- Patient-specificity to improve efficacy of adoptive cell therapy
- Rapid and scalable method of isolating neoantigen-specific TCRs
Yong-Chen W. Lu (NCI), Zhili Zheng (NCI), Peter C. Fitzgerald (NCI), Steven A. Rosenberg (NCI)
- U.S. Provisional: U.S. Provisional Patent Application Number 62/479,398, Filed 31 Mar 2017