Culturing T cells in N-acetyle cysteine (NAC) before they are infused as immunotherapy may improve effectiveness and outcomes in patients with melanoma, according to findings reported in Cancer Research.
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As incidence and mortality rates for melanoma both continue to increase, clinical researchers and health care providers have looked for new ways of treating this patient population. While only 15% of stage IV patients with melanoma survive 5 years when treated with standard treatment, recent studies have shown that up to 40% of stage IV patients survive this long when treated with adoptive cell therapy (ACT), a form of immunotherapy that calls for infusion of autologous, melanoma-specific T-cells. However, patient response is highly variable and better outcomes often correlate with persistence of the transferred cells.
In a study led by Christina Voelkel-Johnson, PhD, Medical University of South Carolina (Charleston, SC), researchers hypothesized that the rapid expansion of harvested T cells before infusion could increase susceptibility to activation-induced cell death, a process that reduces the overall effectiveness of ACT.
Their findings confirmed that theory, as limiting T-cell persistence also limited ACT efficacy. Also, they observed that changing the culture condition by supplementing with NAC improved the survival of the reinfused T cells. Adding NAC to the in vitro T cell expansion culture prevented increases in the DNA damage marker γH2AX and significantly improved T cell persistence and immunotherapy outcomes, including reduced tumor growth and enhanced survival.
Overall, approximately 40% of NAC-cultured T cells were detectable in tumors compared with just 1.2% of standard-culture T cells.
"We were really surprised by the number of adoptively transferred T cells we saw in the tumor," commented Dr Voelkel-Johnson. "Given the harsh environment T cells encounter within tumors, we did not expect that the number of NAC-cultured T cells would be 33-fold higher than T cells not cultured in NAC."
Authors concluded that adding NAC to existing protocols should pose little risk to patients with melanoma while offering some the opportunity to achieve better health outcomes.
