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Formulation de liposomes chargés en Gp100 et Melan-A pour l'immunothérapie du cancer du poumon

Hérin, Caroline
(2015)

Files

ocr-1844352.pdf
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  • 19.03 MB

Details

Supervisors
Loira, Cristina ; Vanbever, Rita
Faculty
Faculté de médecine et médecine dentaire
Degree label
Mémoire de master en sciences pharmaceutiques (finalité spécialisée)
Abstract
The aim of this project is to develop a new immunotherapy approach against lung cancer.The treatment will consist of the pulmonary administration of liposomes-encapsulated tumor antigens and CpG ODN. Liposomes should allow the targeting of antigen presenting cells such as dendritic cells. The local delivery of CpG oligonucleotides and antigens should also increase their therapeutic efficacy.My input in this project was to formulate and characterize liposomes encapsulating the tumor specific antigens. Two antigenic peptides were selected: Gp100 209-217 (2M) and Melan-A 26-35 (2L). They are both immunogenic epitopes that are recognized by T cells and that have been modified in order to increase their immunogenicity.The liposomes formulations had to follow a set of criteria. The size of the liposomes had to be less than 200 nm in order to prevent alveolar macrophage uptake. The liposomes had to be stable and have a high peptide loading rate. An HPLC technique has been developed for the antigen quantification.Several techniques have been used throughout the study to improve the liposome formulations and to allow the co-encapsulation with the CpG: film hydration vs ethanol injection and antigen adsorption vs encapsulation. In order to improve the antigen loading rate, of cationic lipids was increased.Two liposomes formulations were selected at the end of my work. They are respectively made up of DOTAP-DPPC and CD-Chol-DPPC in a 3:1 proportion. They are prepared respectively by film hydration and ethanol injection with a 200µg/mL concentration of Gp100 209-217 (2M) and Melan-A 26-35 (2L). They have led to a successful co-encapsulation with the adjuvant, CpG C274, and will be used in the in-vivo study on B16F10tumor bearing C57B1/6NRJ mice.