Immunoliposomes for Neuroblastoma: Review of the Past Experience and Design of a Novel Nanoparticle
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Published on: September 27, 2024
William S Panosyan1, Daniel E Panosyan2
1University of California Los Angeles, UCLA College of Letters & Science, Los Angeles, CA, U.S.A. williampanosyan@ucla.edu.
Background/Aim:
High-risk/refractory neuro-blastoma (NBL) treatments include anti-GD2-monoclonal antibodies (mAbs). Several immunoliposomes (ILs) covered with anti-GD2-mAbs (GD2-ILs) have been tested pre-clinically. We aimed to review literature on GD2-IL for characteristics of nanoparticles/payloads, conjugation of mAb/fragments and preclinical data, as well as to explore the feasibility of a recently proposed GD2-IL loaded with the antimetabolite oxamate.
Materials And Methods:
Initial PubMed search was generalized for immunoliposomes in cancer. Further search was focused on papers for GD2-IL [keywords: "Immunoliposomes and cancer (or neuroblastoma)"].
Results:
There were 811 results on "immunoliposomes"; >50% were on "immunoliposomes, cancer" (n=439, June 2024). Seventeen items resulted from "immunoliposomes, neuroblastoma" (one was "publishers' correction"). Sixteen GD2-IL references were reviewed (1993-current). The mean±SD GD2-ILs size was 124.8±31 nm (range=86-171). Six papers described GD2-ILs with DNA-damaging agents [doxorubicin (n=4), etoposide (n=1), irinotecan+HDAC inhibitor (n=1)]. Other payloads included: fenretinide (n=4 papers), C-myb antisense (n=2), survivin inhibitor (n=1), tyrosine kinase inhibitor (n=1), IL15 (n=1), and oxamate (n=1). These 9 drug-loads included both hydrophilic and hydrophobic molecules. Except for IL15 and C-myb antisense with high molecular weights (MWs), and oxamate with low MW, the remaining compounds had comparable MWs (496±100 g/mol, range=349-588.6). The overall encapsulation efficiency was 66.2±25.6%. There were 17-30 mAb molecules attached to an IL with PEGylation. Experiments with GD2-positive/GD2-negative cells demonstrated selective efficacy/tropism of GD2-ILs. Mouse models confirmed efficacy, GD2-specific tumor accumulation, decreased toxicity, and improved pharmacokinetic-pharmacodynamics.
Conclusion:
PEGylated anti-GD2-IL may allow NBL tropism. A size of approximately 100 nm could allow vascular permeability and packaging of oxamate in amounts needed for profound/selective lactate dehydrogenase-A inhibition. Thus, oxamate-loaded GD2-ILs may allow exploring the great translational potential of Warburg effect inhibition in GD2-positive cancers.
