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| Item Type: | Article |
|---|---|
| Title: | Isolation of neoantigen-specific human T cell receptors from different human and murine repertoires |
| Creators: |
Grunert, C.  ORCID: https://orcid.org/0000-0001-8376-8629, Willimsky, G. ORCID: https://orcid.org/0000-0002-9693-948X, Peuker, C.A. ORCID: https://orcid.org/0000-0002-0957-2166, Rhein, S. ORCID: https://orcid.org/0000-0002-9445-2352, Hansmann, L. ORCID: https://orcid.org/0000-0003-3790-0128, Blankenstein, T. ORCID: https://orcid.org/0000-0002-3357-4321, Blanc, E. ORCID: https://orcid.org/0000-0002-4369-0254, Beule, D. ORCID: https://orcid.org/0000-0002-3284-0632, Keller, U. ORCID: https://orcid.org/0000-0002-8485-1958, Pezzutto, A. ORCID: https://orcid.org/0000-0002-3246-4470 and Busse, A. ORCID: https://orcid.org/0000-0002-3470-6947
|
| Abstract: | (1) Background: Mutation-specific T cell receptor (TCR)-based adoptive T cell therapy represents a truly tumor-specific immunotherapeutic strategy. However, isolating neoepitope-specific TCRs remains a challenge. (2) Methods: We investigated, side by side, different TCR repertoires-patients' peripheral lymphocytes (PBLs) and tumor-infiltrating lymphocytes (TILs), PBLs of healthy donors, and a humanized mouse model-to isolate neoepitope-specific TCRs against eight neoepitope candidates from a colon cancer and an ovarian cancer patient. Neoepitope candidates were used to stimulate T cells from different repertoires in vitro to generate neoepitope-specific T cells and isolate the specific TCRs. (3) Results: We isolated six TCRs from healthy donors, directed against four neoepitope candidates and one TCR from the murine T cell repertoire. Endogenous processing of one neoepitope, for which we isolated one TCR from both human and mouse-derived repertoires, could be shown. No neoepitope-specific TCR could be generated from the patients' own repertoire. (4) Conclusion: Our data indicate that successful isolation of neoepitope-specific TCRs depends on various factors such as the heathy donor's TCR repertoire or the presence of a tumor microenvironment allowing neoepitope-specific immune responses of the host. We show the advantage and feasibility of using healthy donor repertoires and humanized mouse TCR repertoires to generate mutation-specific TCRs with different specificities, especially in a setting when the availability of patient material is limited. |
| Keywords: | Neoantigens, T Cell Receptor (TCR) Therapy, Tumor-Specific TCR, Antigen-Specific T Cell, T Cell Receptor Repertoire, Animals, Mice |
| Source: | Cancers |
| ISSN: | 2072-6694 |
| Publisher: | MDPI |
| Volume: | 14 |
| Number: | 7 |
| Page Range: | 1842 |
| Date: | 6 April 2022 |
| Official Publication: | https://doi.org/10.3390/cancers14071842 |
| PubMed: | View item in PubMed |
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