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Proteome alteration in Myeloma, MGUS to MM transition

ABSTRACT: We have measured the proteomic changes on ANBL6, IH1, INA6, U266, KJON, OH2, VOLIN, LR5, KARPAS, RAMOS cell lines and used it to build a super SILAC library in order to quantify proteomic changes from MGUG to MM stages of Myeloma with Elite orbitrap mass spetrometer.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Blood Plasma, Cell Culture, Bone Marrow

DISEASE(S): Monoclonal Gammopathy Of Uncertain Significance,Multiple Myeloma

SUBMITTER: Animesh Sharma

LAB HEAD: Geir Slupphaug

PROVIDER: PXD006458 | Pride | 2024-06-07

REPOSITORIES: Pride

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			Action	DRS
	130716_SS_31778MGUS_run1.raw	Raw
	130716_SS_31778MGUS_run2.raw	Raw
	130716_SS_31778MGUS_run3.raw	Raw
	130716_SS_33341MGUS_run1.raw	Raw
	130716_SS_33341MGUS_run2.raw	Raw

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Project description:Background Clinical success of T cell receptor (TCR) gene therapy has previously been demonstrated for NY-ESO-1 TCR gene therapy. To increase numbers of cancer patients that can be treated with TCR gene therapy we aimed to identify a novel set of high-affinity cancer specific TCRs targeting different cancer testis (CT) antigens in prevalent HLA class I alleles. Methods In this study, we selected based on publicly available gene expression databases the most promising CT genes to target. From these selected genes we identified by HLA peptidomics the naturally processed and presented HLA class I peptides. With these peptide-HLA tetramers were generated, and by single cell sorting CT specific CD8+ T cells were selected, and expanded from the allo-HLA repertoire of healthy donors. By several functional assays high avidity CT-specific T cell clones with safe recognition pattern were selected. To evaluate the potential for clinical application in TCR gene therapy, TCRs were sequenced and transferred into peripheral blood derived CD8+ T cells. Results In total we identified, 7 novel CT-specific TCRs that effectively target MAGE-A1, MAGE-A3, MAGE-A6 and MAGE-A9 in the context of human leukocyte antigen(HLA) -A1, -A2, -A3, -B7, -B35 and -C7. TCR gene transfer into CD8⁺ T cells resulted in efficient cytokine production and cytotoxicity of variety of different tumor types without detectable cross-reactivity. In addition, major in vivo antitumor effects of MAGE-A1 specific TCR engineered CD8⁺ T cells was observed in an orthotopic xenograft model for established multiple myeloma, in which bone marrow located tumor cells were completely eradicated after T cell injection. Conclusion The identification of 7 novel CT-specific TCRs, reactive against CT antigens presented in a variety of different HLA class I alleles, allows selection of therapeutic TCRs for an increased number of cancer patients, and will improve development of personalized TCR gene therapy.

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Proteome alteration in Myeloma, MGUS to MM transition

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