Development of synthetic biodegradable microparticulate vaccines: a roller coaster story

Johansen, Pål; Gómez, Julia María Martínez; Gander, Bruno

doi:10.1586/14760584.6.4.471

Cited by 40 publications

(22 citation statements)

References 31 publications

(31 reference statements)

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“…Superior bioavailability and CTL responses associated with the PLGA system can help overcome many of the limitations of current DC-based adoptive immunotherapies (23,24). Key components that need to be optimized prior to employing this novel vaccine strategy in human clinical trials include evaluation of antigen loading and release kinetics, assessment of preclinical safety and estimation of biological potency (25,26).…”

Section: Discussionmentioning

confidence: 99%

Optimization of Stability, Encapsulation, Release, and Cross-Priming of Tumor Antigen-Containing PLGA Nanoparticles

et al. 2012

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Purpose In order to investigate Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP) as potential vehicles for efficient tumor antigen (TA) delivery to dendritic cells (DC), this study aimed to optimize encapsulation/release kinetics before determining immunogenicity of antigen-containing NP. Methods Various techniques were used to liberate TA from cell lines. Single (gp100) and multiple (B16-tumor lysate containing gp100) antigens were encapsulated within differing molecular weight PLGA co-polymers. Differences in morphology, encapsulation/release and biologic potency were studied. Findings were adopted to encapsulate fresh tumor lysate from patients with advanced tumors and compare stimulation of tumor infiltrating lymphocytes (TIL) against that achieved by soluble lysate. Results Four cycles of freeze-thaw + 15 s sonication resulted in antigen-rich lysates without the need for toxic detergents or protease inhibitors. The 80KDa polymer resulted in maximal release of payload and favorable production of immunostimulatory IL-2 and IFN-γ. NP-mediated antigen delivery led to increased IFN-γ and decreased immunoinhibitory IL-10 synthesis when compared to soluble lysate. Conclusions Four cycles of freeze-thaw followed by 15 s sonication is the ideal technique to obtain complex TA for encapsulation. The 80KDa polymer has the most promising combination of release kinetics and biologic potency. Encapsulated antigens are immunogenic and evoke favorable TIL-mediated anti-tumor responses.

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Section: Discussionmentioning

confidence: 99%

Optimization of Stability, Encapsulation, Release, and Cross-Priming of Tumor Antigen-Containing PLGA Nanoparticles

et al. 2012

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“…Polymeric particles, such as poly(lactide-co-glycolide) microspheres and gel particles, currently being explored in antigen delivery, however, strongly suffer from practical drawbacks, including low antigen loading and antigen destruction as a result of the use of organic solvents and harsh reaction conditions, which largely limits their clinical application. [194][195][196][197][198] LbL microcapsules might be interesting antigen-delivery systems because they can efficiently encapsulate proteins under nondenaturing conditions. PMLCs composed of the polyelectrolytes dextran sulfate and poly-l-arginine have been reported to be taken up highly efficiently by dendritic cells derived from mouse bone marrow, without exerting strong toxic effects.…”

Section: Delivery Of Vaccinesmentioning

confidence: 99%

Polymeric Multilayer Capsules in Drug Delivery

et al. 2010

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Recent advances in medicine and biotechnology have prompted the need to develop nanoengineered delivery systems that can encapsulate a wide variety of novel therapeutics such as proteins, chemotherapeutics, and nucleic acids. Moreover, these delivery systems should be "intelligent", such that they can deliver their payload at a well-defined time, place, or after a specific stimulus. Polymeric multilayer capsules, made by layer-by-layer (LbL) coating of a sacrificial template followed by dissolution of the template, allow the design of microcapsules in aqueous conditions by using simple building blocks and assembly procedures, and provide a previously unmet control over the functionality of the microcapsules. Polymeric multilayer capsules have recently received increased interest from the life science community, and many interesting systems have appeared in the literature with biodegradable components and biospecific functionalities. In this Review we give an overview of the recent breakthroughs in their application for drug delivery.

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“…They have been shown to be efficiently phagocytosed by APCs in vivo [135], to prolong antigen presentation by DCs [136], to deliver their antigen cargo to DCs and macrophages for induction of a humoral and cytotoxic Tcell response after systemic and mucosal administration [137][138][139][140][141]. Moreover, PLGA particles are taken up by DCs after intradermal administration in mice even in the absence of immunomodulators, demonstrating their adjuvant activity [142].…”

Section: Biodegradable Polymeric Particlesmentioning

confidence: 99%

VLPs and particle strategies for cancer vaccines

Ungaro

Conte

Quaglia

et al. 2013

Expert Review of Vaccines

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Effective delivery of tumor antigens to APCs is one of the key steps for eliciting a strong and durable immune response to tumors. Several cancer vaccines have been evaluated in clinical trials, based on soluble peptides, but results have not been fully satisfactory. To improve immunogenicity particles provide a valid strategy to display and/or incorporate epitopes which can be efficiently targeted to APCs for effective induction of adaptive immunity. In the present review, we report some leading technologies for developing particulate vaccines employed in cancer immunotherapy, highlighting the key parameters for a rational design to elicit both humoral and cellular responses.

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Development of synthetic biodegradable microparticulate vaccines: a roller coaster story

Cited by 40 publications

References 31 publications

Optimization of Stability, Encapsulation, Release, and Cross-Priming of Tumor Antigen-Containing PLGA Nanoparticles

Optimization of Stability, Encapsulation, Release, and Cross-Priming of Tumor Antigen-Containing PLGA Nanoparticles

Polymeric Multilayer Capsules in Drug Delivery

VLPs and particle strategies for cancer vaccines

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