4473 Immune control of plasma cell disorders – in-depth analysis of Sox2 immunity in MGUS
OBJECTIVES/GOALS: We aim to identify and characterize anti-Sox2-specific CD8+ T cell responses in stable MUGS patients expressing HLA class I alleles-A*02:01 and /or -B*07:02. METHODS/STUDY POPULATION: Cross sectional study of patients with stable MGUS defined as stable serum paraprotein for ≥ 12 mo...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Cambridge University Press
2020-06-01
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| Series: | Journal of Clinical and Translational Science |
| Online Access: | https://www.cambridge.org/core/product/identifier/S2059866120004021/type/journal_article |
| _version_ | 1811155103865896960 |
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| author | Sandra Patricia Susanibar Adaniya Casey L. Cummins Miren L. Baroja Beatriz Carreno Gerald P. Linette Alfred L. Garfall Maya G. Robnett |
| author_facet | Sandra Patricia Susanibar Adaniya Casey L. Cummins Miren L. Baroja Beatriz Carreno Gerald P. Linette Alfred L. Garfall Maya G. Robnett |
| author_sort | Sandra Patricia Susanibar Adaniya |
| collection | DOAJ |
| description | OBJECTIVES/GOALS: We aim to identify and characterize anti-Sox2-specific CD8+ T cell responses in stable MUGS patients expressing HLA class I alleles-A*02:01 and /or -B*07:02. METHODS/STUDY POPULATION: Cross sectional study of patients with stable MGUS defined as stable serum paraprotein for ≥ 12 months from the MM Research Clinic at the Abramson Cancer Institute. Sox2 T cell reactivity will be assessed by IFN-γ ELISPOT assays. Rested PBMC will be pulsed with candidate Sox2-derived peptides predicted to display high affinity to HLA class I alleles and known to be processed and presented as determined by “targeted MS/MS” (mass spectrometry). The presence of anti-Sox2-specific CD8+ T cells will be confirmed in peptide/HLA multimer assays using flow cytometry. Anti-Sox2-specific CD8+ T cells will be characterized for HLA restriction and TCR αβ composition. RESULTS/ANTICIPATED RESULTS: Our work is still in progress. From Aug to Dec 2019, 22 MGUS subjects have been analyzed, 11 of which were found to have the HLA of interest. Positive Sox-2 reactivity by ELISpot was found in 3 subjects. DISCUSSION/SIGNIFICANCE OF IMPACT: Anti-Sox2 immune responses may maintain MGUS in a clinical indolent state by eliminating Sox2-expressing clonogenic MM cells. A detailed characterization of anti-Sox2 T cells followed by in-vivo assessment of their anti-myeloma activity could provide the foundation for a Sox2 based immunotherapy approach in MM. |
| first_indexed | 2024-04-10T04:27:19Z |
| format | Article |
| id | doaj.art-744b69b7b58d490c84824fb69a6f35c4 |
| institution | Directory Open Access Journal |
| issn | 2059-8661 |
| language | English |
| last_indexed | 2024-04-10T04:27:19Z |
| publishDate | 2020-06-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | Journal of Clinical and Translational Science |
| spelling | doaj.art-744b69b7b58d490c84824fb69a6f35c42023-03-10T08:51:36ZengCambridge University PressJournal of Clinical and Translational Science2059-86612020-06-01413613610.1017/cts.2020.4024473 Immune control of plasma cell disorders – in-depth analysis of Sox2 immunity in MGUSSandra Patricia Susanibar Adaniya0Casey L. Cummins1Miren L. Baroja2Beatriz Carreno3Gerald P. Linette4Alfred L. Garfall5Maya G. Robnett6University of Pennsylvania School of MedicineUniversity of Pennsylvania School of MedicineUniversity of Pennsylvania School of MedicineUniversity of Pennsylvania School of MedicineUniversity of Pennsylvania School of MedicineUniversity of Pennsylvania School of MedicineUniversity of Pennsylvania School of MedicineOBJECTIVES/GOALS: We aim to identify and characterize anti-Sox2-specific CD8+ T cell responses in stable MUGS patients expressing HLA class I alleles-A*02:01 and /or -B*07:02. METHODS/STUDY POPULATION: Cross sectional study of patients with stable MGUS defined as stable serum paraprotein for ≥ 12 months from the MM Research Clinic at the Abramson Cancer Institute. Sox2 T cell reactivity will be assessed by IFN-γ ELISPOT assays. Rested PBMC will be pulsed with candidate Sox2-derived peptides predicted to display high affinity to HLA class I alleles and known to be processed and presented as determined by “targeted MS/MS” (mass spectrometry). The presence of anti-Sox2-specific CD8+ T cells will be confirmed in peptide/HLA multimer assays using flow cytometry. Anti-Sox2-specific CD8+ T cells will be characterized for HLA restriction and TCR αβ composition. RESULTS/ANTICIPATED RESULTS: Our work is still in progress. From Aug to Dec 2019, 22 MGUS subjects have been analyzed, 11 of which were found to have the HLA of interest. Positive Sox-2 reactivity by ELISpot was found in 3 subjects. DISCUSSION/SIGNIFICANCE OF IMPACT: Anti-Sox2 immune responses may maintain MGUS in a clinical indolent state by eliminating Sox2-expressing clonogenic MM cells. A detailed characterization of anti-Sox2 T cells followed by in-vivo assessment of their anti-myeloma activity could provide the foundation for a Sox2 based immunotherapy approach in MM.https://www.cambridge.org/core/product/identifier/S2059866120004021/type/journal_article |
| spellingShingle | Sandra Patricia Susanibar Adaniya Casey L. Cummins Miren L. Baroja Beatriz Carreno Gerald P. Linette Alfred L. Garfall Maya G. Robnett 4473 Immune control of plasma cell disorders – in-depth analysis of Sox2 immunity in MGUS Journal of Clinical and Translational Science |
| title | 4473 Immune control of plasma cell disorders – in-depth analysis of Sox2 immunity in MGUS |
| title_full | 4473 Immune control of plasma cell disorders – in-depth analysis of Sox2 immunity in MGUS |
| title_fullStr | 4473 Immune control of plasma cell disorders – in-depth analysis of Sox2 immunity in MGUS |
| title_full_unstemmed | 4473 Immune control of plasma cell disorders – in-depth analysis of Sox2 immunity in MGUS |
| title_short | 4473 Immune control of plasma cell disorders – in-depth analysis of Sox2 immunity in MGUS |
| title_sort | 4473 immune control of plasma cell disorders in depth analysis of sox2 immunity in mgus |
| url | https://www.cambridge.org/core/product/identifier/S2059866120004021/type/journal_article |
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