Culturing T Cells with Anti-Oxidant N-Acetyl Cysteine (NAC) Before Infusion Improves Immunotherapy Effectiveness and Outcomes in Preclinical Model of Melanoma; 33-Fold More NAC-Treated T- Cells Than Untreated T-Cells Observed in Tumor

A collaborative team of investigators at the Medical University of South Carolina (MUSC) and Loyola University (Chicago, Illinois) has demonstrated, for the first time, that culturing T cells in N-acetyl cysteine (NAC) before they are infused as immunotherapy improves effectiveness and outcomes in a preclinical model of melanoma. These findings were reported online on October 15, 2016 in Cancer Research. The article is titled “Efficacy of Adoptive T-Cell Therapy Is Improved by Treatment with the Antioxidant N-Acetyl Cysteine, Which Limits Activation-Induced T-cell Death.” Both the incidence and mortality rates for metastatic melanoma continue to rise. Only about 15% of Stage IV melanoma patients receiving standard treatment can expect to survive for five years. By contrast, clinical trial data show that up to 40% of Stage IV melanoma patients survive for five years when treated with adoptive cell therapy (ACT), a form of immunotherapy that calls for infusion of autologous, melanoma-specific T cells. ACT aims to boost a patient's own immune responses against the cancer. To do this, the patient's own T cells are harvested, genetically modified with a therapeutic T cell receptor, activated, and then rapidly expanded to generate large numbers of T cells for therapeutic re-infusion. Unfortunately, patient responses vary. Better outcomes are positively correlated with persistence of the transferred cells. The rapid expansion of harvested T cells before re-infusion increases their susceptibility to activation-induced cell death (AICD), prompting the authors to hypothesize that AICD reduces ACT's overall effectiveness.
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