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Aliasger SalemAliasger Salem is an associate professor of pharmaceutics and translational therapeutics at the University of Iowa College of Pharmacy.

Therapeutic strategies that involve the manipulation of the host’s immune system are an important facet of cancer research. Antigen-loaded or antigen-coated biodegradable particles (shown below) are capable of being actively taken up by antigen-presenting cells (APCs), and they have shown promising potential in cancer immunotherapy by initiating a strong immunostimulatory 300 nmcascade that results in potent antigen-specific immune responses against the cancer. Such particle based carrier systems offer versatility in that they can simultaneously co-deliver adjuvants with the antigens to enhance APC activation and maturation.

For example, treating mice with biodegradable particles co-loaded with an immunostimulatory adjuvant such as CpG ODN and a model antigen (Ovalbumin/OVA) induced significantly higher amounts of anti-OVA antibody production than other preparations such as the soluble OVA and CpG ODN (P<0.01) and stimulated stronger IgG2a production than delivery of particles entrapping antigen alone.

Biodegradable polymers that can be used to prepare these particles include poly(lactide-co-glycolide) (PLGA) and polyanhydrides. The recent article published by The AAPS Journal entitled Biodegradable Particles as Vaccine Delivery Systems: Size Matters shows findings that the size of particles used to vaccinate mice can affect the magnitude of the antigen-specific immune response stimulated with smaller particles, generating higher antigen-specific cytotoxic T cell responses. Additional findings have shown that combining particle based vaccines with therapies such as cyclophosphamide that suppress regulatory cell populations can further enhance therapeutic efficacy.

Antigen coated biodegradable particles have also shown strong potential as a prime for heterologous prime-boost adenovirus based vaccines generating antigen-specific CD8+ T cell responses that were equally as effective as homologous adenovirus vaccine prime-boosts but with reduced risk of formation of therapy suppressive anti-adenovirus antibodies and other potential adverse effects.

Future research is geared towards combining these particle-based vaccines with other cancer therapy approaches such as surgical resection and chemotherapy to further enhance the therapeutic efficacy against cancers. In terms of the particles themselves, researchers continue to improve the formulation characteristics of the particles including improved loading efficiencies and release profiles and optimizing the sequence of antigen and adjuvant release. In addition, opportunities to modify the surface properties of these particles afford the potential for active targeting properties to APCs and/or enhanced accumulation in solid tumors. Recent advances in these colloidal and particulate systems designed for cancer immunotherapy continue to increase the potential for these systems to translate into clinical cancer vaccines.

What new developments do you anticipate for particle-based vaccines?