Optimizing The Anti-tumoral Efficacy Of Micro-particles Loaded With Innate Inducers.

The immune system can attack abnormal cells such as cancer cells. Immunotherapy, which can be used to treat Cancer is challenging due to the cellular diversity and imposed immune tolerance in the tumor microenvironment (TME). Using innate activators loaded onto micro-particles to induce inflammatory reaction in the TME may present a solution for this problem. Previous studies showed that treating mice with a combination of innate activators loaded onto micro-particles (MP) induced acute inflammatory cytokine and chemokine activity in vitro and in vivo. This study suggested that establishing high quality quantification methods will help to improve the inflammatory reaction in the TME to delay tumor growth. Quantification methods were established for the inducers loaded onto particles. Two inducers; Complement component 5a (C5a) and Lipopolysaccharide (LPS) were tested and optimized. These inducers were loaded on MP, and their effect on the immune activation was evaluated, in vitro on mice splenocytes and in vivo on B16 F10 subcutaneous induced melanoma in C57BL6 mice. LPS quantification was established by using Endosafe PTS Endotoxin Testing System and C5a peptide quantification was established using Q-TOF mass spectrometry. MP loaded with LPS (2.4% of total loading space) and C5a peptide (97.6% of total loading space) showed over 65% reduction in tumor growth rate as compared to non-loaded MP. The results suggest that combining inducers of distinct innate immune activation pathways in certain concentrations holds promise for successful redirection of TME-residing innate immune cells toward anti-tumoral activation.