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Enhanced safety and efficacy profile of CD40 antibody upon encapsulation in pHe-triggered membrane-adhesive nanoliposomes

Year: 2024
Type: article
Abstract: AIM: To develop pH (pHe)-triggered membrane adhesive nanoliposome (pHTANL) of CD40a to enhance anti-tumor activity in pancreatic cancer while reducing systemic toxicity. MATERIALS AND METHODS: A small library of nanoliposomes (NL) with various lipid compositions were synthesized to prepare pH (pHe)-triggered membrane adhesive nanoliposome (pHTANL). Physical and functional characterization of pHTANL-CD40a was performed via dynamic light scattering (DLS), Transmission Electron Microscopy (TEM), confocal microscopy, and flow cytometry. In vivo studies were performed using PDAC (Panc02) transplanted mice. Tumor tissue was analyzed by flow cytometry, and plasma cytokines and liver enzymes were analyzed by ELISA. RESULTS: pHTANL-CD40a reduced tumor growth, enhanced tumor immune infiltration/activation, and enhanced survival compared to vehicle and free-CD40a. Importantly, pHTANL-CD40a treatment resulted in significantly lower systemic toxicity as indicated by unchanged body weight, minimal organ deformity, and reduced serum levels of liver enzyme alanine transaminase (ALT) and inflammatory cytokine IL-6. CONCLUSION: pHTANL-CD40a is more effective than free CD40a in anti-tumor activity, especially in altering the TME immune landscape for a potential therapeutic benefit in combination with immunotherapy.
Source: Nanomedicine
DOI: 10.1080/17435889.2024.2446008
Authors: Salma Althobaiti, Prahlad Parajuli, Duy Luong, Samaresh Sau, Lisa A. Polin, Seongho Kim, Yubin Ge, Arun K. Iyer, Navnath S. Gavande
Language: English
Subfield: Biomaterials
Open Access status: green
Funders: U.S. Department of Defense, Wayne State University, Barbara Ann Karmanos Cancer Institute, DMC Foundation, National Institutes of Health, National Cancer Institute, National Institute of Allergy and Infectious Diseases, Congressionally Directed Medical Research Programs
Awards: A stable path for a core based scientist to advance imaging and cytometry in basic and preclinical research at the Karmanos Cancer Institute, G3542189629, G4119534169, G5850682332, TARGETING DEUBIQUITINASE USP10 TO POTENTIATE IMMUNOTHERAPY IN LUNG CANCER, G6392566495, Tumor Stroma-Penetrating Oligomicelles Containing Combination Payload for Reversal of Drug Resistance and Immune Modulation in Kidney Cancer, G9000149596, G9000190008, CANCER CENTER SUPPORT GRANT, TUMOR STROMA-PENETRATING OLIGOMICELLES CONTAINING COMBINATION PAYLOAD FOR REVERSAL OF DRUG RESISTANCE AND IMMUNE MODULATION IN KIDNEY CANCER
OpenAlex ID: W4405916049
FWCI: 0.334
Cites: 54
Cited by: 4
Related to: 10