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Vaccination Against MSI Colorectal Cancer

ABSTRACT: Patients with advanced microsatellite unstable (MSI-H) colorectal cancer will be vaccinated with three so called frame shift peptides (FSPs), AIM2(-1), HT001(-1) and TAF1B(-1) combined with Montanide ISA-51 VG. By this, an immune response directed against MSI-induced FSPs that are shared by the majority of MSI-H colorectal cancers can be induced. The aim is to show that vaccination against MSI-induced FSPs is safe and can induce or enhance immune responses against MSI-H colorectal cancer-associated antigens.

DISEASE(S): Colorectal Cancer,Colorectal Neoplasms,Advanced Msi-h Colorectal Cancer

PROVIDER: 2114862 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Schistosomiasis continues to be a significant public health problem1. Although vaccine development against this disease has experienced more failures than successes, encouraging results have recently been obtained using membrane-spanning protein antigens from the tegument of S. mansoni. Our group recently identified Sm29, an antigen that is predominantly recognized by IgG1 and IgG3 antibodies of resistant patients2. In the present study, we show that Sm29 is located on the surface of adult worms and lung-stage schistosomula. Immunization of mice with recombinant (r) Sm29 engendered 51% reduction in adult worm burdens, 60% reduction in intestinal eggs and 55% reduction in liver granulomas. Protective immunity in mice was associated with high titers of specific IgG1 and IgG2a and elevated production of IFN-Î³, TNF-Î± and IL-12. Further, cellular responses of infected schistosomiasis patients to rSm29 consisted of elevated IFN-Î³ and an absence of IL-5. Gene expression analysis of worms recovered from rSm29 vaccinated mice relative to control mice revealed a significant (q< 0.01) down-regulation of 498 genes, while no up-regulation was detected. Among down-regulated genes, many of them encode surface antigens and proteins associated with immune signals suggesting that under immune attack schistosomes reduce the expression of critical surface proteins. This study demonstrates that the membrane-bound Sm29 protein is a new molecule that has great potential as a vaccine candidate against schistosomiasis. Keywords: Schistosoma mansoni gene expression in vaccinated mice Two biological samples were used in the study, each used in two arrays (technical replicates with dye swap) and each array containing two replicates of each spot. Overall, there are eight data points data points for each spot. Only cases with more than 4 of 8 points are valid ratios were considered. Value and its respective dye swap value [after changing the log(ratio) signal] were averaged, reducing the data point to four. The average values were than used in the significance testing using SAM (Tusher et al., 2001). The samples were used to get average values using the following combination: 3000139790L with 3000139792L; 3000139790R with 3000139792R; 3000139791L with 3000139795L; 3000139791R with 3000139795R The normalized, averaged dyeswap values are provided in a supplementary file at the foot of the record.

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Vaccination Against MSI Colorectal Cancer

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