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Review
. 2019 Apr 5:10:707.
doi: 10.3389/fimmu.2019.00707. eCollection 2019.

Harnessing Dendritic Cells for Poly (D,L-lactide- co-glycolide) Microspheres (PLGA MS)-Mediated Anti-tumor Therapy

Julia Koerner  1 , Dennis Horvath  1 , Marcus Groettrup  1   2
Affiliations
Review

Harnessing Dendritic Cells for Poly (D,L-lactide- co-glycolide) Microspheres (PLGA MS)-Mediated Anti-tumor Therapy

Julia Koerner et al. Front Immunol. .

Abstract

With emerging success in fighting off cancer, chronic infections, and autoimmune diseases, immunotherapy has become a promising therapeutic approach compared to conventional therapies such as surgery, chemotherapy, radiation therapy, or immunosuppressive medication. Despite the advancement of monoclonal antibody therapy against immune checkpoints, the development of safe and efficient cancer vaccine formulations still remains a pressing medical need. Anti-tumor immunotherapy requires the induction of antigen-specific CD8+ cytotoxic T lymphocyte (CTL) responses which recognize and specifically destroy tumor cells. Due to the crucial role of dendritic cells (DCs) in initiating anti-tumor immunity, targeting tumor antigens to DCs has become auspicious in modern vaccine research. Over the last two decades, micron- or nanometer-sized particulate delivery systems encapsulating tumor antigens and immunostimulatory molecules into biodegradable polymers have shown great promise for the induction of potent, specific and long-lasting anti-tumor responses in vivo. Enhanced vaccine efficiency of the polymeric micro/nanoparticles has been attributed to controlled and continuous release of encapsulated antigens, efficient targeting of antigen presenting cells (APCs) such as DCs and subsequent induction of CTL immunity. Poly (D, L-lactide-co-glycolide) (PLGA), as one of these polymers, has been extensively studied for the design and development of particulate antigen delivery systems in cancer therapy. This review provides an overview of the current state of research on the application of PLGA microspheres (PLGA MS) as anti-tumor cancer vaccines in activating and potentiating immune responses attempting to highlight their potential in the development of cancer therapeutics.

Keywords: CTL; PLGA; anti-tumor response; cancer vaccine; dendritic cell; immunotherapy; microspheres; spray drying.

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Figures

Figure 1
Figure 1
Chemical structure of the poly (D,L – lactide-co-glycolide) (PLGA) co-polymer.
Figure 2
Figure 2
Schematic illustration of the spray drying process for preparation of PLGA microspheres. The sample emulsion is spray-atomized into small droplets at the nozzle. These droplets in the heated dry air flow are transformed into dry particles by evaporation of the organic solvent. The particles are then separated from the drying medium and collected under constant low pressure as dry powder in the lower collection vessel.
Figure 3
Figure 3
Schematic description of PLGA microsphere mediated anti-tumor response. After subcutaneous immunization, PLGA microspheres are efficiently taken up by immature, skin-resident APCs, mainly DCs. Co-delivery of antigens and TLR ligands leads to enhanced DC activation and maturation by upregulation of co-stimulatory surface maturation marker and MHC class molecules I and II during migration to lymph nodes. In the draining lymph node, encapsulated cancer antigens are processed and presented on either MHC class II to naive CD4+ T helper cells or via cross presentation to CD8+ T cells. Priming and activation of CD8+ T cells leads to differentiation and proliferation of tumor antigen-specific effector CTLs. Clonal expansion and CTL infiltration into the tumor environment results in recognition and eradication of target tumor cells mediated via IFN-γ release and enhanced Th1 polarized immune functions.
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