Polymeric microparticles for sustained and local delivery of antiCD40 and antiCTLA-4 in immunotherapy of cancer

摘要: This study investigated the feasibility of use polymeric microparticles for sustained and local delivery immunomodulatory antibodies in immunotherapy cancer. Local potent avoids unwanted systemic side effects while retaining their anti-tumor effects. Microparticles based on poly(lactic-co-hydroxymethyl-glycolic acid) (pLHMGA) loaded with two distinct types (CTLA-4 antibody blocking inhibitory receptors T cells or CD40 agonistic stimulating dendritic cells) were prepared by double emulsion solvent evaporation technique. The obtained particles had a diameter 12-15 μm to avoid engulfment phagocytes slightly porous as shown SEM analysis. loading efficiency was >85%. vitro release profile antiCD40 antiCTLA-4 from showed burst about 20% followed content up 80% around 30 days. therapeutic efficacy microparticulate formulations studied colon carcinoma tumor model (MC-38). Mice bearing subcutaneous MC-38 tumors treated same dose formulated either incomplete Freund's adjuvant (IFA) microparticles. antibody-loaded comparable IFA formulation no adverse biodegradable fully resorbed vivo remnants inflammatory depots observed present cured mice. Moreover exhibited lower serum levels comparison which lowers probability In conclusion, pLHMGA are excellent systems providing long-lasting non-toxic therapy