Low-Toxicity Natural Killer Cell-Based Immunotherapy for NRAS-Driven Mucosal Melanoma: Advances in Immune Regenerative Medicine.

Abstract

Anorectal mucosal melanoma (AMM) poses a significant challenge as a rare and aggressive cancer with limited treatment options. The current standard treatments for AMM have notable drawbacks, often leading to disease recurrence and progression, ultimately resulting in a poor prognosis for patients with advanced AMM. The critical necessity for innovative therapeutic strategies to enhance outcomes in AMM cases is evident. In this report, a groundbreaking personalized (n) of one approach was detailed for the treatment of advanced mucosal melanoma. This pioneering method involves utilizing low-dose immunotherapy as an immune regenerative medicine (IRM) regimen. The treatment plan is tailored based on liquid biopsy analysis of plasma-derived cell-free circulating tumor DNA (ctDNA) with mutational profiling. This approach aims to enhance the patient's immune response to the disease, reduce tumor burden, and minimize adverse effects. This compelling case study showcased a 66-year-old male with recurrent stage III AMM. Despite undergoing standard therapies with multiple surgeries, radiation therapy, and immune checkpoint inhibitor (ICI) treatment, disease progression persisted. However, post low-dose interleukin-2 (IL-2) immunotherapy, notable improvements were observed in the patient's immune function, particularly in natural killer (NK) cell number and activity. Additionally, the cancer exhibited regression, highlighted by a significant decrease in NRAS Q61R driver mutations and the absence of the BRCA2 A3012P mutation. These encouraging results suggest that personalized precision immunotherapy focusing on NK cells could potentially revolutionize the treatment landscape for AMM patients who have exhausted conventional therapies. Notably, the patient experienced minimal side effects and avoided toxicity-related complications. While further research is essential to validate these findings, the prospect of this approach as a viable management strategy for this aggressive cancer type is promising.