Particle platforms for cancer immunotherapy

Abstract

Elevated understanding and respect for the relevance of the immune system in cancer development and therapy has led to increased development of immunotherapeutic regimens that target existing cancer cells and provide long-term immune surveillance and protection from cancer recurrence. This review discusses using particles as immune adjuvants to create vaccines and to augment the anticancer effects of conventional chemotherapeutics. Several particle prototypes are presented, including liposomes, polymer nanoparticles, and porous silicon microparticles, the latter existing as either single-or multiparticle platforms. The benefits of using particles include immune-cell targeting, codelivery of antigens and immunomodulatory agents, and sustained release of the therapeutic payload. Nanotherapeutic-based activation of the immune system is dependent on both intrinsic particle characteristics and on the immunomodulatory cargo, which may include danger signals known as pathogen-associated molecular patterns and cytokines for effector-cell activation.

Sequential delivery of an anticancer drug and combined immunomodulatory nanoparticles for efficient chemoimmunotherapy

“…The activity of immune cells, such as dendritic cells (DCs), macrophages, natural killer cells, and T-cells, is enhanced by various immune activators, including cytokines, immune adjuvants, and Tolllike receptor (TLR) ligands. [23][24][25][26] The TLR ligand unmethylated cytosine-phosphate-guanosine oligodeoxynucleotide (CpG ODN) binds to TLR9 receptors on the endosomal membranes of DCs or macrophages and consequently activates the immune response by inducing the secretion of various cytokines. 27,28 These immune responses can increase anticancer activity by generating T helper 1 (Th1) cells and cytotoxic T-lymphocytes (CTLs); however, these responses simultaneously result in the expression of anti-inflammatory cytokines that downregulate the secretion of Th1 cytokines, major histocompatibility complex class II antigens, and costimulatory molecules from DCs or macrophages.…”

Development and Evaluation of Biodegradable Particles Coloaded With Antigen and the Toll-Like Receptor Agonist, Pentaerythritol Lipid A, as a Cancer Vaccine

“…The reasons for delivering PET lipid A in particles are to increase its stability and to favor phagocytosis by antigen presenting cells, such as, DCs, thus potentiating increased adjuvant efficiency whilst simultaneously reducing its impact on other off-target cell types that may express TLR-4. Polymeric particles have been proven to be a valuable vehicle for delivering antigen and/or adjuvants to DCs to initiate antigen-specific immune responses [39, 40]. Soluble PET lipid A has been shown previously to possess potentially potent adjuvant properties by stimulating CD40 and CD86 up-regulation by murine dendritic cells in a manner comparable to LPS [7].…”

Biodegradable polymeric microsphere-based vaccines and their applications in infectious diseases

“…67 Nanoparticles have also been discussed in the context of cancer immunotherapy. 76 Because the 2 size classes of polymeric particles have different properties, 77 different applications of microspheres and nanoparticles should be considered according to their advantages and disadvantages. For example, DCs preferentially take up nanoparticles over microparticles.…”