PLGA Nanoencapsulation Enhances Immunogenicity of Heat-Shocked Melanoma Tumor Cell Lysates

Therapeutic cancer vaccines have emerged as promising immunotherapy approaches. TRIMEL, a heat-shocked lysate derived from three melanoma cell lines, constitutes the basis of TAPCells and TRIMELVax cancer vaccines, both of which have shown clinical efficacy but face major limitations in stability and logistics due to the requirement of ultra-low temperature storage. In this study, we evaluated the encapsulation of TRIMEL into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP-TRIMEL) as a strategy to enhance stability and preserve immunogenic function under more feasible storage conditions. NP-TRIMEL was synthesized using a double-emulsion method and characterized by hydrodynamic size, zeta potential, morphology, and TRIMEL loading. Functional assays using melanoma patient-derived monocytes and peripheral blood lymphocytes suggested that NP-TRIMEL promoted the generation of TAPCells capable of inducing cytotoxic lymphocytes against allogeneic melanoma cells, even after 24 weeks of storage at 4 °C. Remarkably, NP-TRIMEL showed a two-order-of-magnitude increase in efficiency compared to the original TRIMEL in promoting TAPCells differentiation and lymphocyte activation. These findings provide evidence that tumor cell lysates can be functionally stabilized and even potentiated through nanoencapsulation, reinforcing the concept that delivery platforms not only preserve but also enhance antigen-driven immune responses.