Dataset Information

Characterization of a Cytomegalovirus-Specific T Lymphocyte Product Obtained Through a Rapid and Scalable Production Process for Use in Adoptive Immunotherapy.

ABSTRACT: Immunosuppressed patients are susceptible to virus reactivation or de novo infection. Adoptive immunotherapy, based on virus-specific T lymphocytes (VST), can prevent or treat viral diseases. However, donor availability, HLA-compatibility restrictions, high costs, and time required for the production of personalized medicines constitute considerable limitations to this treatment. Ex vivo rapid and large-scale expansion of VST, compliant with current good manufacturing practice (cGMP) standards, with an associated cell donor registry would overcome these limitations. This study aimed to characterize a VST product obtained through an expansion protocol transferable to cGMP standards. Antigenic stimulus consisted of cytomegalovirus (CMV) pp65 peptide pool-pulsed autologous dendritic cells (DCs) derived from monocytes. G-Rex technology, cytokines IL-2, IL-7, and IL-15, and anti-CD3 and anti-CD28 antibodies were used for culture. At day 14 of cell culture, the final product was characterized regarding T cell subsets, specificity, and functionality. The final product, comprised mainly CD4+ and CD8+ T lymphocytes (49.2 ± 24.7 and 42.3 ± 25.2, respectively). The culture conditions made it possible to achieve at least a 98.89-fold increase in pp65-specific CD3+ IFN-?+ cells. These cells were specific, as pp65-specific cytotoxicity was demonstrated. Additionally, in complete HLA mismatch and without the presence of pp65, alloreactivity resulted in <5% cell lysis. In conclusion, a cGMP scalable process for the generation of a large number of doses of CMV-specific cytotoxic T cells was successfully performed.

SUBMITTER: Grau-Vorster M

PROVIDER: S-EPMC7052482 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Characterization of a Cytomegalovirus-Specific T Lymphocyte Product Obtained Through a Rapid and Scalable Production Process for Use in Adoptive Immunotherapy.

Grau-Vorster Marta M López-Montañés María M Cantó Ester E Vives Joaquim J Oliver-Vila Irene I Barba Pere P Querol Sergi S Rudilla Francesc F

Frontiers in immunology 20200225

Immunosuppressed patients are susceptible to virus reactivation or <i>de novo</i> infection. Adoptive immunotherapy, based on virus-specific T lymphocytes (VST), can prevent or treat viral diseases. However, donor availability, HLA-compatibility restrictions, high costs, and time required for the production of personalized medicines constitute considerable limitations to this treatment. <i>Ex vivo</i> rapid and large-scale expansion of VST, compliant with current good manufacturing practice (cGM ...[more]

PMID: 32161589

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Project description:The generation of highly-reactive T lymphocytes against tumor-associated antigens remains an obstacle for effective adoptive immunotherapy of cancer. Recently, we found that microRNA-181a (miR-181a) acts as an intrinsic modulator of T cell antigen sensitivity in a transgenic T cell line in vitro. This molecule is part of a growing family of evolutionarily selected small interfering RNA that control gene expression at the posttranscriptional level by targeting messenger RNA (mRNA) for degradation or translational repression. Here, we explored the use of miR-181a to improve anti-tumor T cell responsiveness against weakly immunogenic tumor-associated antigens. We found that genetic engineering of T lymphocytes with miR-181a dramatically augmented the function of poorly responsive human tumor-infiltrating lymphocytes and TCR-engineered peripheral blood lymphocytes, resulting in potent anti-tumor reactivity. Furthermore, in a mouse model, miR-181a increased the function of self/tumor-specific CD8+ T cells enabling effective tumor destruction in the absence of vaccination or exogenous cytokines that were otherwise essential requirements and thus represents a significant advance over previous approaches. Although miRNAs have been previously shown to play critical functional roles in the development and function of vertebrate immune systems and pathogenesis of cancer, this report comprises the first use of a miRNA gene as tool in the treatment of disease. Keywords: cellular modification design For the 6 mouse samples the Operon Array-Ready Oligo Set (AROSâ¢) V 4.0 contains 35,852 longmer probes representing 25,000 genes and about 38,000 gene transcripts and also includes 380 controls platform was used and each sample was hybridized in duplicate. For the 6 human samples, the human cDNA microarray platform was used which consist of 17 k cDNA array included a combination from a RG_HsKG_031901 7 k clone set and 10,000 clones from the RG_Hs_seq_ver_070700 40 k clone set (Research Genetics, Huntsville, AL). The cDNA clones include 12,072 uniquely named genes, 875 duplicates of named genes.

Dataset Information

Characterization of a Cytomegalovirus-Specific T Lymphocyte Product Obtained Through a Rapid and Scalable Production Process for Use in Adoptive Immunotherapy.

Publications

Characterization of a Cytomegalovirus-Specific T Lymphocyte Product Obtained Through a Rapid and Scalable Production Process for Use in Adoptive Immunotherapy.

Similar Datasets

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