In-vivo enhanced anti-tumor efficacy of CAR reinforced macrophages (CAR-PS-sLNPs)

Описание: Gist: In-vivo antitumor efficacy of the CAR-PS-sLNPs are also carried out in B16F10 bearing mouse. Intratumoral injection of the lipid nanoparticles (LNPs) at the tumor site with mCherry reporter gene in mouse, shows signal specific to tumor site after 24 hr of injection (figure 5a). In the case of LNP without PS CAR are also expressed in the tumor whereas in the CAR-PS-sLNP shows expression mainly in the tumor associated macrophages (TAM) due to the macrophages specific PS (figure 5b). Thereafter phenotypic changes of the macrophages are also evaluated and observed that M1 type phenotype markers are expressed significantly higher in CAR-PS-sLNPs (figure 5c) along with more MHC-II expression in the same case (figure 5d). Thereafter antitumor efficacy was evaluated in which LNPs are injected three times on alternate days (figure 5e). Maximum tumor suppression is being observed in the final optimized CAR construct (figure 5f) with no other toxicity observed in any LNPs case as body weight remains same (figure 5g). Survival rate is also high in the optimized CAR construct with sting agonist. While the total number of macrophages remains same however, M1 type phenotype increases in the CAR construct with sting agonist indicating the reprogramming ability to shift TAM to M1 type macrophages (figure 5i, j, k). Myeloid derived suppressor cells of MDSCs are also decreased significantly in the optimized CAR construct (figure 5l). More infiltration of the CD8+ T cells was found in optimized CAR construct (figure 5 m) along with more activating CD8+ T cells (figure 5 n). These all indicates the enhanced antitumor efficacy and specificity to target TAM.

#cancer #cancertreatment #cancerawareness #solidtumor #invivo #cartherapy #carmacrophages #CARmtherapy #stingagoinst #immunesystem #immuneresponse #immunotherapy #biology #macrophages #phagocytosis #proinflammatorycytokines #antigenpresentation #tam #tumorassociatedmacrophages #eatmesignal #phosphatidylserine #lipidnanoparticles #lnp #phenotypic #immunomodulation #antitumor #antigenpresentation #cd8tcells #myeloidderivedsuppressorcells #mdsc #mhc2 #specificity #invivo

Reference:
https://doi.org/10.1021/acsnano.5c09138