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A First-in-Human Study of SON-DP in Participants With Relapsed/Refractory Intolerant to Standard of Care Therapies for Advanced/Metastatic Solid Tumors

ABSTRACT: This proposed Phase I clinical trial of SON-DP is an FIH, open-label, Phase Ia/Ib dose escalation and expansion study to evaluate the safety, tolerability, PK, and PD of SON-DP in participants with relapsed/refractory/intolerant to standard of care therapies, for advanced/ metastatic solid tumors.

DISEASE(S): Ovarian Cancer,Solid Tumor,Colorectal Cancer,Colorectal Neoplasms,Pancreatic Cancer,Ovarian Neoplasms,Pancreatic Neoplasms,Breast Cancer

PROVIDER: 69608 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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MHC Class Ib-restricted CD8+ T Cells Possess Strong Tumoricidal Activities

Project description:The tumoricidal effects of CD8+T cells are well acknowledged, but how MHC Ib-restricted CD8+T (Ib-CD8+T) cells contribute to anti-tumor immunity remains obscure. Here, we show that infusion of MHC Ia+ cells to Kb-/-Db-/- mice induced the expansion of Ib-CD8+T cells in tumors and potently inhibited tumor progression. Such priming of Ib-CD8+T cells by MHC-Ia is not MHC haplotype restricted and MHC Ia tetramers alone can prime Ib-CD8+T cells for activation. The MHC Ia priming promoted Tbet expression in Ib-CD8+T cells and in absence of Tbet, such priming effect diminished. Importantly, these tumoricidal Ib-CD8+T cells are positive for CX3CR1, and exhibit rapid proliferation, high expression of cytotoxic factors, and prolonged persistence at tumor sites. Adoptive transfer of CX3CR1+Ib-CD8+T cells to wild type mice resulted in potent anti-tumor effects. Our findings unravel an uncharacterized function of MHC Ia molecules in immunoregulation and raise the possibility of using Ib-CD8+T cells in tumor immunotherapy.

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mRNA gene expression analysis of 104 early stage non-small cell lung cancers

Project description:104 early-stage (IA and IB) non-small cell lung cancers were evaluated with the Illumina Human HT-12 v4 BeadChip.

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Epigenetic reprogramming in relapsed childhood ALL

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Epigenetic reprogramming in relapsed childhood ALL

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Analysis of non-relapsed and relapsed adult type granulosa cell tumors suggests stable transcriptomes during tumor progression

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Gene expression in FIH-1 silenced human nucleus pulposus cells

Project description:To evaluate the effect of Hypoxia-inducible factor 1-alpha inhibitor (HIF-1) in nucleus pulposus (NP) cells, human NP cells were lentivirally transduced with either control or FIH-1 targeted shRNA. Gene expression changes between samples from control and FIH-1 silenced cells were evaluated using a microarray. Primary NP cells were isolated from human discs and grown in culture. Cells were transduced with either control or FIH-1 targeting shRNA constructs. Silencing of FIH-1 was confirmed for each set using qRT-PCR and Western blot. Total RNA from NP cells was used for RNA extraction and hybridization on the Affymetrix microarray. Control samples: C1, C2, and C3 and FIH-1-silenced samples: E1, E2, and E3.

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