Process Development for Adoptive Cell Therapy in Academia: A Pipeline for Clinical-Scale Manufacturing of Multiple TCR-T Cell Products

Silva, DN (author)

Chrobok, M (author)

Rovesti, G (author)

Healy, K (author)

Maravelia, P (author)

Gatto, F (author)

Mazza, M (author)

Mazzotti, L (author)

Lohmann, V (author)

(creator_code:org_t)

2022-06-16
2022
English.
In: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13, s. 896242-

Related links:: http://kipublication...; show more...; https://doi.org/10.3...; show less...

Abstract Subject headings

Cellular immunotherapies based on T cell receptor (TCR) transfer are promising approaches for the treatment of cancer and chronic viral infections. The discovery of novel receptors is expanding considerably; however, the clinical development of TCR-T cell therapies still lags. Here we provide a pipeline for process development and clinical-scale manufacturing of TCR-T cells in academia. We utilized two TCRs specific for hepatitis C virus (HCV) as models because of their marked differences in avidity and functional profile in TCR-redirected cells. With our clinical-scale pipeline, we reproduced the functional profile associated with each TCR. Moreover, the two TCR-T cell products demonstrated similar yield, purity, transduction efficiency as well as phenotype. The TCR-T cell products had a highly reproducible yield of over 1.4 × 109 cells, with an average viability of 93%; 97.8–99% of cells were CD3+, of which 47.66 ± 2.02% were CD8+ T cells; the phenotype was markedly associated with central memory (CD62L+CD45RO+) for CD4+ (93.70 ± 5.23%) and CD8+ (94.26 ± 4.04%). The functional assessments in 2D and 3D cell culture assays showed that TCR-T cells mounted a polyfunctional response to the cognate HCV peptide target in tumor cell lines, including killing. Collectively, we report a solid strategy for the efficient large-scale manufacturing of TCR-T cells.

By the author/editor: Silva, DN; Chrobok, M; Rovesti, G; Healy, K; Wagner, AK; Maravelia, P; show more...; Gatto, F; Mazza, M; Mazzotti, L; Lohmann, V; Chen, MS; Sallberg, M; Buggert, M; Pasetto, A; show less...

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