Mimicking Pathogens to Augment the Potency of Liposomal Cancer Vaccines

Abstract

Liposomes have emerged as interesting vehicles in cancer vaccination strategies as their composition enables the inclusion of both hydrophilic and hydrophobic antigens and adjuvants. In addition, liposomes can be decorated with targeting moieties to further resemble pathogenic particles that allow for better engagement with the immune system. However, so far liposomal cancer vaccines have not yet reached their full potential in the clinic. In this review, we summarize recent preclinical studies on liposomal cancer vaccines. We describe the basic ingredients for liposomal cancer vaccines, tumor antigens, and adjuvants, and how their combined inclusion together with targeting moieties potentially derived from pathogens can enhance vaccine immunogenicity. We discuss newly identified antigen-presenting cells in humans and mice that pose as promising targets for cancer vaccines. The lessons learned from these preclinical studies can be applied to enhance the efficacy of liposomal cancer vaccination in the clinic.

Incorporation of Toll-Like Receptor Ligands and Inflammasome Stimuli in GM3 Liposomes to Induce Dendritic Cell Maturation and T Cell Responses

“…As controls, we prepared liposomes that did not contain any adjuvant (referred to as control), or contained only the oxidized lipid PGPC or only MDP (Supplementary Figures 1A, B). In addition, liposomes were without targeting ligand or contained the ganglioside GM3 (annotated with squares or circles, respectively) to facilitate specific uptake by CD169-expressing cells (18,48,49,58,59). The liposomes exhibited a similar mean size, in the range of 160-190 nm and a PDI below 0.2, indicating a relatively homogenous size distribution and the zeta-potential was negative, around -50 mV (Supplementary Figures 1A, B).…”

“…GM3 liposomes bind to both human and mouse CD169expressing cells (18,48,49,58,59). We first determined the capacity of the liposomes to be taken up and to activate human CD169-expressing APCs.…”

“…Furthermore, liposomes can be surface-decorated with targeting moieties, to facilitate cellular targeting (16,17). Thus, by use of liposomes and combining both antigen and adjuvant in a single particle that is targeted to a cell of interest in vivo, the potency of cancer vaccination is expected to be augmented (18)(19)(20).…”

“…A recently described alternative cellular target for cancer vaccines are CD169-expressing macrophages (18). These cells are strategically located in the spleen to capture particulate antigen and marked by their high expression of CD169, also known as Siglec-1 or sialoadhesin (35)(36)(37)(38).…”

COVID-19 mRNA vaccines and pathological cell-cell fusion: an unintended consequence

“…To deliver the liposome cargo to human immune cells, mRNA therapeutics must trick host phagocytes into internalizing LNPs by phagocytosis [80,81]. This is accomplished by decorating the liposomal particles with ionizable lipids and DSPC, an anionic phospholipid that mimics ePS and conveys readiness for phagocytosis [82,83].…”