"M\u00E9lanome -- Dissertation universitaire" . . . "Hydroxyethylstarch microparticles adjuvants properties. Application in anti-melanoma immunotherapy" . "Text" . . "2007" . "Hydroxy\u00E9thylamidons -- Dissertation universitaire" . "Capsules -- Dissertation universitaire" . "@Malignant melanoma is on the rise in fair-skinned societies. The discovery of melanoma-associated antigens by T cells led to the development of new active approaches of immunotherapy. We have tested a new strategy of anti-melanoma immunotherapy. To do that, hydroxyethylstarch (HES) microparticles were designed and used to encapsulate proteins extracted from a doxorubicin-resistant B16 murine melanoma cell line (B16R). The aim of this strategy was to improve protein presentation to antigen-presenting cells and therefore increase their immunogenicity. We have demonstrated that HES microparticles exhibit the required features for peptide or protein delivery systems, such as biocompatibility and biodegradability. Moreover, they are easy to produce and to use for loading of antigens. We have studied the adjuvant properties of HES microparticles on the immune response against bovine serum albumin (BSA). These particles 1) are not immunogenic, 2) can be internalized by mononuclear cells, 3) enhance the immune response against BSA, and 4) induce both Th1 and Th2-mediated responses. We have shown that subcutaneous prophylactic injections of free or encapsulated B16R proteins induced a weak slowing down in tumour development. Immunological studies revealed that this impair tumour growth was correlated with high levels of CD8 T cells in the treated animals. Since B16R cells do not express class I molecules both in vitro and in vivo, the reduction of tumour growth was not mediated by a specific cellular immune response. Moreover the cytolitic activity of spleen cells was higher when the target cells expressed MHC class I molecules. These results highlight the significant part of MHC class I molecules in the establishment of an effective anti-tumour immunity." . "Th\u00E8ses et \u00E9crits acad\u00E9miques" . . "Antig\u00E8nes -- Dissertation universitaire" . "Cellules pr\u00E9sentatrices d'antig\u00E8ne -- Dissertation universitaire" . "Immunoth\u00E9rapie -- Dissertation universitaire" . . . . . . . . "Les propri\u00E9t\u00E9s adjuvantes des microcapsules d\u2019hydroxy\u00E9thyl amidon. Application en immunoth\u00E9rapie anti-m\u00E9lanome" . "Devant l\u2019augmentation de fr\u00E9quence du m\u00E9lanome et la d\u00E9couverte des antig\u00E8nes associ\u00E9s aux tumeurs sugg\u00E9rant un r\u00F4le du syst\u00E8me immunitaire dans le traitement du cancer, de nouvelles approches d\u2019immunoth\u00E9rapies actives pour la pr\u00E9vention et le traitement du m\u00E9lanome ont \u00E9t\u00E9 d\u00E9velopp\u00E9es. Nous avons test\u00E9 une strat\u00E9gie d\u2019immunoth\u00E9rapie anti-m\u00E9lanome par injection de prot\u00E9ines solubles extraites de cellules de m\u00E9lanome murin B16 r\u00E9sistantes \u00E0 la doxorubicine (B16R) encapsul\u00E9es ou non dans des microcapsules d\u2019hydroxy\u00E9thyl amidon (HEA). Cette strat\u00E9gie a \u00E9t\u00E9 r\u00E9alis\u00E9e dans le but d\u2019am\u00E9liorer la pr\u00E9sentation des prot\u00E9ines aux cellules pr\u00E9sentatrices d\u2019antig\u00E8nes (CPA) et ainsi augmenter leur immunog\u00E9nicit\u00E9. Nous avons montr\u00E9 que les microcapsules d\u2019HEA sont, entre autre, biocompatibles, biod\u00E9gradables, faciles \u00E0 produire et \u00E0 utiliser pour le chargement des antig\u00E8nes. Ces propri\u00E9t\u00E9s int\u00E9ressantes sugg\u00E8rent leur utilisation in vivo en tant que syst\u00E8me de lib\u00E9ration/pr\u00E9sentation de peptides ou prot\u00E9ines. Nous nous sommes int\u00E9ress\u00E9s aux propri\u00E9t\u00E9s adjuvantes des microcapsules sur la r\u00E9ponse immunitaire anti-s\u00E9rum albumine bovine (SAB). Elles sont 1) immunologiquement inertes, 2) capables d\u2019\u00EAtre internalis\u00E9es par des cellules mononucl\u00E9\u00E9es, 3) de potentialiser la r\u00E9ponse immunitaire contre la SAB, et 4) d\u2019induire \u00E0 la fois une r\u00E9ponse de type Th1 et Th2. Nous avons montr\u00E9 que les injections prophylactiques sous-cutan\u00E9es de prot\u00E9ines B16R encapsul\u00E9es ou non ralentissent le d\u00E9veloppement tumoral. L\u2019\u00E9tude des m\u00E9canismes immunitaires impliqu\u00E9s dans ces ralentissements montre l\u2019induction d\u2019une r\u00E9ponse humorale anti-cellules B16R avec un nombre de cellules CD8 sup\u00E9rieur chez les animaux pr\u00E9trait\u00E9s. Les cellules B16R in vitro et in vivo n\u2019expriment pas de mol\u00E9cule de Classe I, les ralentissements de la progression tumorale ne peuvent donc pas \u00EAtre dus \u00E0 l\u2019induction d\u2019une r\u00E9ponse immunitaire cellulaire sp\u00E9cifique. De plus, les activit\u00E9s cytolytiques des cellules spl\u00E9niques sont sup\u00E9rieures lorsque les cellules cibles expriment des mol\u00E9cules de Classe I. Ces r\u00E9sultats mettent en \u00E9vidence le r\u00F4le important des mol\u00E9cules de classe I dans l\u2019\u00E9tablissement d\u2019une immunit\u00E9 anti-tumorale sp\u00E9cifique efficace" . . . . "Les propri\u00E9t\u00E9s adjuvantes des microcapsules d\u2019hydroxy\u00E9thyl amidon. Application en immunoth\u00E9rapie anti-m\u00E9lanome" . . .