The Lab focuses on tumour immunology and liposome targeting.
Liposomes are synthetic nanoparticles each typically composed of a spherical phospholipid bilayer ~100 nm diameter. These phospholipid structures can readily be made to encapsulate and carry hydrophilic drugs and other agents within their central aqueous core and hydrophilic drugs or agents embedded in the lipid bi-layer. The potential for liposomes to be used for therapies such as cancer therapy has been exploited by the development of “stealth” liposomes (which have reduced non-specific binding to blood components), and technology we recently developed to enable convenient engraftment of ligands such as proteins and/or peptides onto their exterior surface, to promote targeting of the liposomes to cells expressing the cognate receptors.
Utilising murine tumour models we recently showed that engraftment of ligands that target antigen-containing liposomes to receptors on antigen-presenting cells can elicit more effective antigen specific anti-tumour responses, thereby providing a more effective approach for immunotheraies and vaccine development. Similarly, engraftment of peptides that target receptors on tumour cells and/or the tumour vasculature onto liposomes containing doxorubicin can enhance therapeutic efficacy, compared to non-targeted doxorubicin.
At least two factors still limit the effectiveness of liposomes as as therapeutics, however. Firstly, while the inclusion of the polyethylene-glycol derivatives in “stealth” liposomes substantially reduces their non-specific binding and uptake by phagocytes of the reticulo-endothelial system (RES), the half-life of these liposomes in the blood circulation (~48hrs) is still limited. and target delivery losses due to RES uptake is still substantial. Secondly, efficient delivery of targeted stealth liposomes to tumours is highly limited due to the difficulty of liposomes and drugs in the blood circulation to readily penetrate tumours.
The current research priority for my group are to develop and implement strategies both to further reduce the non-specific uptake of liposomes by phagocytes in the circulation, and to enhance the tumour penetrability of targeted liposomes.
- Faham, Abdus; Altin, Joseph G.Ag-bearing liposomes engrafted with peptides that interact with CD11c/CD18 induce potent Ag-specific and antitumor immunity International Journal of Cancer. 129(6), 1391-1403.
- Herringson, Thomas P.; Altin, Joseph G. Effective tumor targeting and enhanced anti-tumor effect of liposomes engrafted with peptides specific for tumor lymphatics and vasculature, International Journal of Pharmaceutics. 411(1-2), 206-214.
- Herringson, Thomas P.; Altin, Joseph G. Increasing the antitumor efficacy of doxorubicin-loaded liposomes with peptides anchored via a chelator lipid Journal of Drug Targeting. 19(8), 681-689.
- Faham, Abdus; Herringson, Thomas; Parish, Chris; et al pDNA-lipoplexes engrafted with flagellin-related peptide induce potent immunity and anti-tumour effects Vaccine. 29(40), 6911-6919.
- Faham, A.; Altin, J. G.Antigen-Containing Liposomes Engrafted with Flagellin-Related Peptides Are Effective Vaccines That Can Induce Potent Antitumor Immunity and Immunotherapeutic Effect Journal of Immunology 185(3), 1744-1754.
- Altin JG, Parish CR, Price J, Atmosukarto I, and De Wildt RM. Composition for targeting dendritic cells.
- Herringson, T. P.; Altin, J. G.Convenient targeting of stealth siRNA-lipoplexes to cells with chelator lipid-anchored molecules Journal of Controlled Release 139(3), 229-238.
- Faham, A; Bennett, D; Altin, J. G. Liposomal Ag engrafted with peptides of sequence derived from HMGB1 induce potent Ag-specific and anti-tumour immunity Vaccine. 27(42), 5846-5854.
- Hamazah, J; Altin, J. G.; Herrington, T; et al. Targeted Liposomal Delivery of TLR9 Ligands Activates Spontaneous Antitumor Immunity in an Autochthonous Cancer Model Journal of Immunology. 183(2), 1091-1098
- Herringson, T. P.; Patlolla, R. R.; Altin, J. G.Targeting of plasmid DNA-lipoplexes to cells with molecules anchored via a metal chelator lipid Journal of Gene Medicine. 11(11), 1048-1063.