Technology Bundle ID: NCI-E-067-2017

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

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Primary Inventors: 
Yong-Chen Lu (NCI)
Co-Inventors: 
Peter Fitzgerald (NCI), Steven Rosenberg (NCI), Zhili Zheng (NCI)
Application: 
Therapeutics
Development Status: 

Pre-clinical (in vivo)

Institute or Center: 
NCI

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.

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

Patents

US Provisional Application 62/479,398
Filed on 2017-03-31

Updated

Oct 6, 2017

Data Source: 
nci