A Rapid Method of Isolating Neoantigen-specific T Cell Receptor Sequences

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.

Competitive Advantages:

• 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

Commercial Applications:

• Personalized immunotherapy to treat cancer patients
• ​Research tool to identify mutation-specific T-cell receptors