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. 2025 Jan;20(2):155-166.
doi: 10.1080/17435889.2024.2446008. Epub 2024 Dec 29.

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

Salma Althobaiti  1 , Prahlad Parajuli  1   2 , Duy Luong  1 , Samaresh Sau  1 , Lisa A Polin  2   3 , Seongho Kim  3 , Yubin Ge  2   3 , Arun K Iyer  1   4 , Navnath S Gavande  1   2
Affiliations

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

Salma Althobaiti et al. Nanomedicine (Lond). 2025 Jan.

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.

Keywords: CD40 agonist antibody (CD40a); Immunotherapy; Pancreatic ductal adenocarcinoma (PDAC); nanoliposomes; pHe-triggered membrane adhesive.

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Conflict of interest statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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