AI Article Synopsis
- The study focuses on developing an effective cell therapy using donor-derived cytotoxic T lymphocytes (CTL) to target leukemia in pediatric patients following a specific type of stem cell transplant (HSCT).
- Researchers optimized the generation of these CTLs by using interferon-treated dendritic cells and adding IFNα2b during the priming phase, leading to improved T cell responses.
- Quality control tests confirmed that the produced CTLs were safe, effective, and capable of attacking leukemia cells, demonstrating a reproducible and standardized method for creating anti-leukemia therapies.
Article Abstract
Background Aims: Somatic cell therapy based on the infusion of donor-derived cytotoxic T lymphocytes (CTL) able to recognize patients' leukemia blasts (LB) is a promising approach to control leukemia relapse after allogeneic HSCT. The success of this approach strongly depends on the ex vivo generation of high-quality donor-derived anti-leukemia CTL in compliance with Good Manufacturing Practices (GMP). We previously described a procedure for generating large numbers of donor-derived anti-leukemia CTL through stimulation of CD8-enriched lymphocytes with dendritic cells (DCs) pulsed with apoptotic LB in the presence of interleukin (IL)-12, IL-7 and IL-15. Here we report that the use of IFN-DC and the addition of IFNα2b during the priming phase significantly improve the generation of an efficient anti-leukemia T cells response in vitro.
Methods: Using this approach, 20 high-risk pediatric patients given haploidentical HSCT for high-risk acute leukemia were enrolled and 51 batches of advanced therapy medical products (ATMP), anti-leukemia CTL, were produced.
Results: Quality controls demonstrated that all batches were sterile, free of mycoplasma and conformed to acceptable endotoxin levels. Genotype analysis confirmed the molecular identity of the ATMP based on the starting biological material used for their production. The majority of ATMP were CD3+/CD8+ cells, with a memory/terminal activated phenotype, including T-central memory populations. ATMP were viable after thawing, and most ATMP batches displayed efficient capacity to lyse patients' LB and to secrete interferon-γ and tumor necrosis factor-α.
Conclusions: These results demonstrated that our protocol is highly reproducible and allows the generation of large numbers of immunologically safe and functional anti-leukemia CTL with a high level of standardization.
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| http://dx.doi.org/10.1016/j.jcyt.2024.04.005 | DOI Listing |
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