LB998 Lymph node delivery of immunstimulatory agent monophosphoryl lipid A via bioadhesive nanoparticles in the treatment of cutaneous melanoma

Monophosphoryl lipid A (MPLA) is a low-toxicity derivative of LPS with immunomodulating properties. Nanoparticle (NP) encapsulation immunomodulatory agents may allow for effective delivery to tumor sites as well draining lymph nodes (TDLN) and stimulation anti-tumor immune responses while minimizing systemic side effects. Our bioadhesive NP (BNP) platform has been used chemotherapy drugs enhanced efficacy in pre-clinical models solid tumors including SCC. To evaluate the cellular association retention BNP TDLN, we flow cytometry assess cell uptake after in-vivo intratumoral (i.t.) Cy5-BNP established PDVC57 SCC tumors. were present 58.4 ± 9.7% TDLN dendritic cells (DC) 62.1 7.7% CD68+ macrophages (Mac) 24 hr post injection, sustained one week administration (DC: 13.9 1.2%, Mac 23.1 0.8%), <1% DC or contralateral LN Cy5+ at either timepoint. We then examined whether MPLA activity affected by measuring NF-kB inducibility THP-1 monocytes. observed equivalent dose-dependent induction free BNP-MPLA. also assessed bone marrow-derived (BMDC) maturation found that BNP-MPLA superior (57.0% CD11c+MHCII+) 48 (65.7%) incubation relative doses (24 hr: 51.5%, 59%, p= 0.0040). further inhibition melanoma growth vivo using immunogenic YUMMER1.7 model. Tumor bearing mice received two once weekly i.t. injections BNP-MPLA, MPLA, vehicle. treated showed significantly reduced volume, resolution 12.5% mice, improved survival (vehicle v p =0.8147, vehicle 0.0076, 0.0060). These results suggest be effectively delivered help promote response against local melanoma.