Direct identification of neoantigen-specific TCRs from tumor specimens by high-throughput single-cell sequencing
| Autor: | Jared J. Gartner, Yong-Chen Lu, Paul F. Robbins, Steven A. Rosenberg, Frank J. Lowery, Todd D. Prickett, Zhili Zheng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
lymphocytes
0301 basic medicine Cancer Research medicine.medical_treatment T cell Immunology Receptors Antigen T-Cell chemical and pharmacologic phenomena Computational biology cell engineering Biology adoptive gastrointestinal neoplasms 03 medical and health sciences 0302 clinical medicine Cancer immunotherapy Antigens Neoplasm melanoma medicine Humans Immunology and Allergy Receptor RC254-282 Pharmacology Immune Cell Therapies and Immune Cell Engineering integumentary system Melanoma T-cell receptor High-Throughput Nucleotide Sequencing Neoplasms. Tumors. Oncology. Including cancer and carcinogens hemic and immune systems Immunotherapy tumor-infiltrating medicine.disease Autologous T-cells 030104 developmental biology medicine.anatomical_structure Oncology Single cell sequencing 030220 oncology & carcinogenesis Molecular Medicine immunotherapy |
| Zdroj: | Journal for ImmunoTherapy of Cancer, Vol 9, Iss 7 (2021) Journal for Immunotherapy of Cancer |
| ISSN: | 2051-1426 |
| Popis: | BackgroundRecognition of neoantigens by T cells plays a major role in cancer immunotherapy. Identification of neoantigen-specific T-cell receptors (TCRs) has become a critical research tool for studying T cell-mediated responses after immunotherapy. In addition, neoantigen-specific TCRs can be used to modify the specificity of T cells for T cell-based therapies targeting tumor-specific mutations. Although several techniques have been developed to identify TCR sequences, these techniques still require a significant amount of labor, making them impractical in the clinical setting.MethodsThanks to the availability of high-throughput single-cell sequencing, we developed a new process to isolate neoantigen-specific TCR sequences. This process included the isolation of tumor-infiltrating T cells from a tumor specimen and the stimulation of T cells by neoantigen-loaded dendritic cells, followed by single-cell sequencing for TCR and T-cell activation markers, interferon-γ and interleukin-2.ResultsIn this study, potential neoantigen-specific TCRs were isolated from three melanoma and three colorectal tumor specimens. These TCRs were then synthesized and transduced into autologous T cells, followed by testing the recognition of neoantigens. A total of 28 neoantigen-specific TCRs were identified by this process. If identical TCR sequences were detected from two or more single cells, this approach was highly reliable (100%, 19 out of 19 TCRs).ConclusionThis single-cell approach provides an efficient process to isolate antigen-specific TCRs for research and clinical applications. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|