Investigation of a new tumor-associated glycosylated antigen as target for dendritic cell vaccination in pancreatic cancer

Glycoproteins, as valuable targets for dendritic cell (DC)-vaccination in cancers, remain an open question. Glycosylated structures, which are aberrantly modified during cancerisation, impact positively or negatively on glycoprotein immunogenicity. Here is presented an oncofetal glycovariant of bile-salt-dependent-lipase, expressed on human tumoral pancreas and efficiently processed by DC’s, inducing T-lymphocyte activation

Bases fondamentales d une immunothérapie des cancers du pancréas exocrine par activation des cellules dendritiques

Le cancer du pancréas exocrine, un des plus agressifs, présente un diagnostic tardif et reste peu sensible aux traitements conventionnels. Il est donc essentiel de développer de nouvelles approches diagnostiques et thérapeutiques de ce cancer. Nous avons mis en évidence l expression par la cellule tumorale pancréatique des glycotopes J28 et 16D10 portés par les glycoisoformes pathologiques de la Lipase Sels Biliaires Dépendante (BSDLp-J28, BSDLp-16D10). Cette expression nous a permis d envisager une approche d immunothérapie des cancers du pancréas basée sur l activation des cellules dendritiques (DC) par une BSDLp-J28. Ainsi, nous avons déterminé les mécanismes de capture et de transport de la BSDLp-J28 par les DC et montré que cette BSDLp-J28 pouvait induire en partie la maturation des DC permettant l activation des lymphocytes T naïfs. De plus, avons également produit et purifié le glycotope J28 recombinant afin de l utiliser en immunothérapie. Enfin, après avoir identifié la BSDL dans les urines de sujets sains, nous avons montré la présence de la BSDLp-J28 dans les urines de sujets atteints d adénocarcinomes pancréatiques.AIX-MARSEILLE3-BU Sc.St Jérô (130552102) / SudocSudocFranceF

Monoclonal Antibody 16D10 to the C-Terminal Domain of the Feto-Acinar Pancreatic Protein Binds to Membrane of Human Pancreatic Tumoral SOJ-6 Cells and Inhibits the Growth of Tumor Xenografts

Feto-acinar pancreatic protein (FAPP) characterized by mAbJ28 reactivity is a specific component associated with ontogenesis and behaves as an oncodevelopment-associated antigen. We attempted to determine whether pancreatic tumoral SOJ-6 cells are expressed at their surface FAPP antigens and to examine if specific antibodies directed against these FAPP epitopes could decrease the growth of pancreatic tumors in a mice model. For this purpose, we used specific antibodies against either the whole FAPP, the O-glycosylated C-terminal domain, or the N-terminal domain of the protein. Our results indicate that SOJ-6 cells expressed at their surface a 32-kDa peptide corresponding to the C-terminal domain of the FAPP. Furthermore, we show, by using endoproteinase Lys-C or geldanamycin, a drug able to impair the FAPP secretion, that this 32-kDa peptide expressed on the SOJ-6 cell surface comes from the degradation of the FAPP. Finally, an in vivo prospective study using a preventative tumor model in nude mice indicates that targeting this peptide by the use of mAb16D10 inhibits the growth of SOJ-6 xenografts. The specificity of mAb16D10 for pancreatic tumors and the possibility to obtain recombinant structures of mucin-like peptides recognized by mAb16D10 and mAbJ28 are promising tools in immunologic approaches to cure pancreatic cancers

Strong coupling between a photon and a hole spin in silicon

Spins in semiconductor quantum dots constitute a promising platform for scalable quantum information processing. Coupling them strongly to the photonic modes of superconducting microwave resonators would enable fast non-demolition readout and long-range, on-chip connectivity, well beyond nearest-neighbor quantum interactions. Here we demonstrate strong coupling between a microwave photon in a superconducting resonator and a hole spin in a silicon-based double quantum dot issued from a foundry-compatible MOS fabrication process. By leveraging the strong spin-orbit interaction intrinsically present in the valence band of silicon, we achieve a spin-photon coupling rate as high as 330 MHz largely exceeding the combined spin-photon decoherence rate. This result, together with the recently demonstrated long coherence of hole spins in silicon, opens a new realistic pathway to the development of circuit quantum electrodynamics with spins in semiconductor quantum dots

Strong coupling between a photon and a hole spin in silicon

Spins in semiconductor quantum dots constitute a promising platform for scalable quantum information processing. Coupling them strongly to the photonic modes of superconducting microwave resonators would enable fast non-demolition readout and long-range, on-chip connectivity, well beyond nearest-neighbor quantum interactions. Here we demonstrate strong coupling between a microwave photon in a superconducting resonator and a hole spin in a silicon-based double quantum dot issued from a foundry-compatible MOS fabrication process. By leveraging the strong spin-orbit interaction intrinsically present in the valence band of silicon, we achieve a spin-photon coupling rate as high as 330 MHz largely exceeding the combined spin-photon decoherence rate. This result, together with the recently demonstrated long coherence of hole spins in silicon, opens a new realistic pathway to the development of circuit quantum electrodynamics with spins in semiconductor quantum dots