Abstract
Adoptive transfer of T cells genetically engineered with a T cell receptor (TCR) is a promising cancer treatment modality that requires the identification of TCRs with good characteristics. Most T cell cloning methods involve a stringent singularization process, which necessitates either tedious hands-on operations or high cost. We present an efficient and nonstringent cloning approach based on existing techniques. We hypothesize that after elimination of most nonspecific T cells, a clonotype with high quality could outcompete other clonotypes and finally form a predominant population. This TCR identification method can be used to clone virus-specific TCRs efficiently from cancer patients and is easily adoptable by any laboratory.
Highlights
Viral infections cause approximately 10–12% of all human malignancies worldwide
At least 8 viruses have been associated with human cancers, including Epstein-Barr virus (EBV), papillomavirus (HPV), Kaposi’s sarcoma-associated herpesvirus (KSHV), Merkel cell polyomavirus (MCV), hepatitis B virus (HBV), human T lymphotropic virus type-1 (HTLV-1), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) [1]
T cell receptor (TCR) discovery has played a key role in the development of effective TCR-T cell therapy
Summary
Viral infections cause approximately 10–12% of all human malignancies worldwide. To date, at least 8 viruses have been associated with human cancers, including Epstein-Barr virus (EBV), papillomavirus (HPV), Kaposi’s sarcoma-associated herpesvirus (KSHV), Merkel cell polyomavirus (MCV), hepatitis B virus (HBV), human T lymphotropic virus type-1 (HTLV-1), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) [1]. In the life cycle of some viruses, especially EBV and HPV, virus-derived oncogenic proteins are always present in malignant cells, making them excellent targets for T cells. All. EBV-associated cancers express some EBV latency antigens (EBNA1, EBNA2, EBNA3-3C, EBNA-LP, LMP1 and LMP2) [4]. EBV-associated cancers express some EBV latency antigens (EBNA1, EBNA2, EBNA3-3C, EBNA-LP, LMP1 and LMP2) [4] These intracellular or membrane proteins can be processed and presented on the host cell surface in the context of MHC molecules and recognized by T cell receptors (TCRs) as foreign antigens. Compared with traditional cancer therapies, adoptive T-cell therapies (ACTs) may have unique advantages in eradicating virus-associated malignancies [5, 6]
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