Particulate based vaccines for cancer immunotherapy

Rosalia, R.A. (2014)

Doctoral Thesis

In this thesis we describe our studies aimed at optimizing the efficacy of synthetic long peptide (SLP) vaccines via the encapsulation in Poly-(lactic-co-glycolic acid) (PLGA)particles. Immunotherapy based on SLP-vaccines has resulted in strong tumor specific immune response and importantly, improved clinical benefit in patients with pre-malignant lesions. One important drawback associated with SLP-vaccines is their current form of administration in Montanide, a clinical grade water-in-oil emulsion. The aim of this Ph.D project was to device an alternative method of delivery which overcomes the drawbacks associated with the use of Montanide. For this purpose we explored the use of PLGA (nano)particles (NP) as a delivery vehicle for SLP. Several important aspects for vaccination were assessed in this thesis; from the pharmaceutical formulation to the immunological characterization of different PLGA-SLP preparations. Together, the data presented in this thesis show that PLGA-NP mediated delivery of SLP is a very efficient method to target, load and mature Dendritic cells (DCs) as immune stimulatory compounds can be co-encapsulated with the vaccine Ag

• CTL
• Cross-presentation
• PLGA
• SLP
• Dendritic cells

• All authors: Rosalia, R.A.
• Supervisor: Guchelaar, H.J.; Ossendorp, F.
• Co-supervisor: Oostendorp, J.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2014-10-02
• ISBN (print): 9789492026026
• Sponsorship: Financial support for the publication of this thesis was provided by AZL Onderzoeks- en Ontwikkelingskrediet Apotheek, and ISA Pharmaceuticals, Leiden, The Netherlands