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Neoantigen-specific stimulation of tumor-infiltrating lymphocytes enables effective TCR isolation and expansion while preserving stem-like memory phenotypes

J Immunother Cancer. 2024-05; 
Noam Levin, Sanghyun P Kim, Charles A Marquardt, Nolan R Vale, Zhiya Yu, Sivasish Sindiri, Jared J Gartner, Maria Parkhurst, Sri Krishna, Frank J Lowery, Nikolaos Zacharakis, Lior Levy, Todd D Prickett, Tiffany Benzine, Satyajit Ray, Robert V Masi, Billel Gasmi, Yong Li, Rafiqul Islam, Alakesh Bera, Stephanie L Goff, Paul F Robbins, Steven A Rosenberg
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Gene Synthesis … despite their stem-like gene expression profiles might be different … Other exhaustion-associated genes that had been … NheI and EcoRI (custom cloning by GenScript). Class II HLAs were … Get A Quote

摘要

background: Tumor-infiltrating lymphocytes (TILs) targeting neoantigens can effectively treat a selected set of metastatic solid cancers. However, harnessing TILs for cancer treatments remains challenging because neoantigen-reactive T cells are often rare and exhausted, and ex vivo expansion can further reduce their frequencies. This complicates the identification of neoantigen-reactive T-cell receptors (TCRs) and the development of TIL products with high reactivity for patient treatment. methods: We tested whether TILs could be in vitro stimulated against neoantigens to achieve selective expansion of neoantigen-reactive TILs. Given their prevalence, mutant p53 or RAS were studied as models of human neoantigens... More

关键词

Adoptive cell therapy - ACT, T cell Receptor - TCR, Tumor infiltrating lymphocyte - TIL