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Ginny L. Bumgardner - One of the best experts on this subject based on the ideXlab platform.

  • anTibody suppressor cd8 T Cells require cxcr5
    Transplantation, 2019
    Co-Authors: Jason M Zimmerer, Bryce A Ringwald, Steven M Elzein, Christina L Avila, Robert T Warren, Mahmoud Abdelrasoul, Ginny L. Bumgardner
    Abstract:

    BACKGROUND We previously reporTed The novel acTiviTy of alloprimed CD8 T Cells ThaT suppress posTTransplanT alloanTibody producTion. The purpose of The sTudy is To invesTigaTe The expression and role of CXCR5 on anTibody-suppressor CD8 T-cell funcTion. METHODS C57BL/6 mice were TransplanTed wiTh FVB/N hepaTocyTes. Alloprimed CD8 T Cells were reTrieved on day 7 from hepaTocyTe TransplanT recipienTs. UnsorTed or flow-sorTed (CXCR5CXCR3 and CXCR3CXCR5) alloprimed CD8 T-cell subseTs were analyzed for in viTro cyToToxiciTy and capaciTy To inhibiT in vivo alloanTibody producTion following adopTive Transfer inTo C57BL/6 or high alloanTibody-producing CD8 knock ouT (KO) hepaTocyTe TransplanT recipienTs. AlloanTibody TiTer was assessed in CD8 KO mice reconsTiTuTed wiTh naive CD8 T Cells reTrieved from C57BL/6, CXCR5 KO, or CXCR3 KO mice. AnTibody suppression by ovalbumin (OVA)-primed monoclonal OVA-specific T-cell recepTor Transgenic CD8+ T Cells (OT-I) CXCR5 or CXCR3 CD8 T-cell subseTs was also invesTigaTed. RESULTS Alloprimed CXCR5CXCR3CD8 T Cells mediaTed in viTro cyToToxiciTy of alloprimed "self" B Cells, while CXCR3CXCR5CD8 T Cells did noT. Only flow-sorTed alloprimed CXCR5CXCR3CD8 T Cells (noT flow-sorTed alloprimed CXCR3CXCR5CD8 T Cells) suppressed alloanTibody producTion and enhanced grafT survival when Transferred inTo TransplanT recipienTs. Unlike CD8 T Cells from wild-Type or CXCR3 KO mice, CD8 T Cells from CXCR5 KO mice do noT develop alloanTibody-suppressor funcTion. Similarly, only flow-sorTed CXCR5CXCR3 (and noT CXCR3CXCR5) OVA-primed OT-I CD8 T Cells mediaTed in vivo suppression of anTi-OVA anTibody producTion. CONCLUSIONS These daTa supporT The conclusion ThaT expression of CXCR5 by anTigen-primed CD8 T Cells is criTical for The funcTion of anTibody-suppressor CD8 T Cells.

  • anTibody suppressor cd8 T Cells require cxcr5
    Transplantation, 2019
    Co-Authors: Jason M Zimmerer, Bryce A Ringwald, Steven M Elzein, Christina L Avila, Robert T Warren, Mahmoud Abdelrasoul, Ginny L. Bumgardner
    Abstract:

    BACKGROUND We previously reporTed The novel acTiviTy of alloprimed CD8 T Cells ThaT suppress posTTransplanT alloanTibody producTion. The purpose of The sTudy is To invesTigaTe The expression and role of CXCR5 on anTibody-suppressor CD8 T-cell funcTion. METHODS C57BL/6 mice were TransplanTed wiTh FVB/N hepaTocyTes. Alloprimed CD8 T Cells were reTrieved on day 7 from hepaTocyTe TransplanT recipienTs. UnsorTed or flow-sorTed (CXCR5CXCR3 and CXCR3CXCR5) alloprimed CD8 T-cell subseTs were analyzed for in viTro cyToToxiciTy and capaciTy To inhibiT in vivo alloanTibody producTion following adopTive Transfer inTo C57BL/6 or high alloanTibody-producing CD8 knock ouT (KO) hepaTocyTe TransplanT recipienTs. AlloanTibody TiTer was assessed in CD8 KO mice reconsTiTuTed wiTh naive CD8 T Cells reTrieved from C57BL/6, CXCR5 KO, or CXCR3 KO mice. AnTibody suppression by ovalbumin (OVA)-primed monoclonal OVA-specific T-cell recepTor Transgenic CD8+ T Cells (OT-I) CXCR5 or CXCR3 CD8 T-cell subseTs was also invesTigaTed. RESULTS Alloprimed CXCR5CXCR3CD8 T Cells mediaTed in viTro cyToToxiciTy of alloprimed "self" B Cells, while CXCR3CXCR5CD8 T Cells did noT. Only flow-sorTed alloprimed CXCR5CXCR3CD8 T Cells (noT flow-sorTed alloprimed CXCR3CXCR5CD8 T Cells) suppressed alloanTibody producTion and enhanced grafT survival when Transferred inTo TransplanT recipienTs. Unlike CD8 T Cells from wild-Type or CXCR3 KO mice, CD8 T Cells from CXCR5 KO mice do noT develop alloanTibody-suppressor funcTion. Similarly, only flow-sorTed CXCR5CXCR3 (and noT CXCR3CXCR5) OVA-primed OT-I CD8 T Cells mediaTed in vivo suppression of anTi-OVA anTibody producTion. CONCLUSIONS These daTa supporT The conclusion ThaT expression of CXCR5 by anTigen-primed CD8 T Cells is criTical for The funcTion of anTibody-suppressor CD8 T Cells.

Yongping Song - One of the best experts on this subject based on the ideXlab platform.

  • Clinical Trials of dual-TargeT CAR T Cells, donor-derived CAR T Cells, and universal CAR T Cells for acuTe lymphoid leukemia
    BMC, 2019
    Co-Authors: Juanjuan Zhao, Yongping Song, Delong Liu
    Abstract:

    AbsTracT The currenT TreaTmenT for pediaTric acuTe lymphoblasTic leukemia (ALL) is highly successful wiTh high cure raTe. However, The TreaTmenT of adulT ALL remains a challenge, parTicularly for refracTory and/or relapsed (R/R) ALL. The advenT of new TargeTed agenTs, blinaTumomab, inoTuzumab ozogamycin, and chimeric anTigen recepTor (CAR) T Cells, are changing The TreaTmenT paradigm for ALL. Tisagenlecleucel (kymriah, NovarTis) is an auTologous CD19-TargeTed CAR T cell producT approved for TreaTmenT of R/R B cell ALL and lymphoma. In an aTTempT To reduce The relapse raTe and TreaT Those relapsed paTienTs wiTh anTigen loss, donor-derived CAR T Cells and CD19/CD22 dual-TargeT CAR T Cells are in clinical Trials. Gene-ediTed “off-The-shelf” universal CAR T Cells are also undergoing acTive clinical developmenT. This review summarized new clinical Trials and laTesT updaTes aT The 2018 ASH Annual MeeTing on CAR T Therapy for ALL wiTh a focus on dual-TargeT CAR T and universal CAR T cell Trials

  • Universal CARs, universal T Cells, and universal CAR T Cells
    Journal of Hematology & Oncology, 2018
    Co-Authors: Juanjuan Zhao, Yongping Song
    Abstract:

    CurrenTly, The Two approved T cell producTs wiTh chimeric anTigen recepTors (CAR) are from auTologous T Cells. These CAR T Cells approved for clinical use musT be generaTed on a cusTom-made basis. This case-by-case auTologous T cell producTion plaTform remains a significanT limiTing facTor for large-scale clinical applicaTion due To The cosTly and lengThy producTion process. There is also an inherenT risk of producTion failure. The individualized, cusTom-made auTologous CAR T cell producTion process also posTs consTricTion on The wide applicaTion on diverse Tumor Types. Therefore, universal allogeneic T Cells are needed for The preparaTion of universal CAR T Cells ThaT can serve as The “off-The-shelf” ready-To-use TherapeuTic agenTs for large-scale clinical applicaTions. Genome-ediTing Technologies including ZFN (zinc finger nuclease), TALEN (TranscripTion acTivaTor-like effecTor nuclease), and CRISPR-Cas9 are being used To generaTe The universal Third-parTy T Cells. In addiTion, spliT, universal, and programmable (SUPRA) CARs are being developed To enhance The flexibiliTy and conTrollabiliTy of CAR T Cells. The engineered universal T Cells and universal CARs are paving The road for a ToTally new generaTion of CAR T Cells capable of TargeTing mulTiple anTigens and/ or being delivered To mulTiple recipienTs wiThouT re-ediTing of T Cells. This may escalaTe To a new wave of revoluTion in cancer immunoTherapy. This review summarized The laTesT advances on designs and developmenT of universal CARs, universal T Cells, and clinical applicaTion of universal CAR T Cells.

Jason M Zimmerer - One of the best experts on this subject based on the ideXlab platform.

  • anTibody suppressor cd8 T Cells require cxcr5
    Transplantation, 2019
    Co-Authors: Jason M Zimmerer, Bryce A Ringwald, Steven M Elzein, Christina L Avila, Robert T Warren, Mahmoud Abdelrasoul, Ginny L. Bumgardner
    Abstract:

    BACKGROUND We previously reporTed The novel acTiviTy of alloprimed CD8 T Cells ThaT suppress posTTransplanT alloanTibody producTion. The purpose of The sTudy is To invesTigaTe The expression and role of CXCR5 on anTibody-suppressor CD8 T-cell funcTion. METHODS C57BL/6 mice were TransplanTed wiTh FVB/N hepaTocyTes. Alloprimed CD8 T Cells were reTrieved on day 7 from hepaTocyTe TransplanT recipienTs. UnsorTed or flow-sorTed (CXCR5CXCR3 and CXCR3CXCR5) alloprimed CD8 T-cell subseTs were analyzed for in viTro cyToToxiciTy and capaciTy To inhibiT in vivo alloanTibody producTion following adopTive Transfer inTo C57BL/6 or high alloanTibody-producing CD8 knock ouT (KO) hepaTocyTe TransplanT recipienTs. AlloanTibody TiTer was assessed in CD8 KO mice reconsTiTuTed wiTh naive CD8 T Cells reTrieved from C57BL/6, CXCR5 KO, or CXCR3 KO mice. AnTibody suppression by ovalbumin (OVA)-primed monoclonal OVA-specific T-cell recepTor Transgenic CD8+ T Cells (OT-I) CXCR5 or CXCR3 CD8 T-cell subseTs was also invesTigaTed. RESULTS Alloprimed CXCR5CXCR3CD8 T Cells mediaTed in viTro cyToToxiciTy of alloprimed "self" B Cells, while CXCR3CXCR5CD8 T Cells did noT. Only flow-sorTed alloprimed CXCR5CXCR3CD8 T Cells (noT flow-sorTed alloprimed CXCR3CXCR5CD8 T Cells) suppressed alloanTibody producTion and enhanced grafT survival when Transferred inTo TransplanT recipienTs. Unlike CD8 T Cells from wild-Type or CXCR3 KO mice, CD8 T Cells from CXCR5 KO mice do noT develop alloanTibody-suppressor funcTion. Similarly, only flow-sorTed CXCR5CXCR3 (and noT CXCR3CXCR5) OVA-primed OT-I CD8 T Cells mediaTed in vivo suppression of anTi-OVA anTibody producTion. CONCLUSIONS These daTa supporT The conclusion ThaT expression of CXCR5 by anTigen-primed CD8 T Cells is criTical for The funcTion of anTibody-suppressor CD8 T Cells.

  • anTibody suppressor cd8 T Cells require cxcr5
    Transplantation, 2019
    Co-Authors: Jason M Zimmerer, Bryce A Ringwald, Steven M Elzein, Christina L Avila, Robert T Warren, Mahmoud Abdelrasoul, Ginny L. Bumgardner
    Abstract:

    BACKGROUND We previously reporTed The novel acTiviTy of alloprimed CD8 T Cells ThaT suppress posTTransplanT alloanTibody producTion. The purpose of The sTudy is To invesTigaTe The expression and role of CXCR5 on anTibody-suppressor CD8 T-cell funcTion. METHODS C57BL/6 mice were TransplanTed wiTh FVB/N hepaTocyTes. Alloprimed CD8 T Cells were reTrieved on day 7 from hepaTocyTe TransplanT recipienTs. UnsorTed or flow-sorTed (CXCR5CXCR3 and CXCR3CXCR5) alloprimed CD8 T-cell subseTs were analyzed for in viTro cyToToxiciTy and capaciTy To inhibiT in vivo alloanTibody producTion following adopTive Transfer inTo C57BL/6 or high alloanTibody-producing CD8 knock ouT (KO) hepaTocyTe TransplanT recipienTs. AlloanTibody TiTer was assessed in CD8 KO mice reconsTiTuTed wiTh naive CD8 T Cells reTrieved from C57BL/6, CXCR5 KO, or CXCR3 KO mice. AnTibody suppression by ovalbumin (OVA)-primed monoclonal OVA-specific T-cell recepTor Transgenic CD8+ T Cells (OT-I) CXCR5 or CXCR3 CD8 T-cell subseTs was also invesTigaTed. RESULTS Alloprimed CXCR5CXCR3CD8 T Cells mediaTed in viTro cyToToxiciTy of alloprimed "self" B Cells, while CXCR3CXCR5CD8 T Cells did noT. Only flow-sorTed alloprimed CXCR5CXCR3CD8 T Cells (noT flow-sorTed alloprimed CXCR3CXCR5CD8 T Cells) suppressed alloanTibody producTion and enhanced grafT survival when Transferred inTo TransplanT recipienTs. Unlike CD8 T Cells from wild-Type or CXCR3 KO mice, CD8 T Cells from CXCR5 KO mice do noT develop alloanTibody-suppressor funcTion. Similarly, only flow-sorTed CXCR5CXCR3 (and noT CXCR3CXCR5) OVA-primed OT-I CD8 T Cells mediaTed in vivo suppression of anTi-OVA anTibody producTion. CONCLUSIONS These daTa supporT The conclusion ThaT expression of CXCR5 by anTigen-primed CD8 T Cells is criTical for The funcTion of anTibody-suppressor CD8 T Cells.

Juanjuan Zhao - One of the best experts on this subject based on the ideXlab platform.

  • Clinical Trials of dual-TargeT CAR T Cells, donor-derived CAR T Cells, and universal CAR T Cells for acuTe lymphoid leukemia
    BMC, 2019
    Co-Authors: Juanjuan Zhao, Yongping Song, Delong Liu
    Abstract:

    AbsTracT The currenT TreaTmenT for pediaTric acuTe lymphoblasTic leukemia (ALL) is highly successful wiTh high cure raTe. However, The TreaTmenT of adulT ALL remains a challenge, parTicularly for refracTory and/or relapsed (R/R) ALL. The advenT of new TargeTed agenTs, blinaTumomab, inoTuzumab ozogamycin, and chimeric anTigen recepTor (CAR) T Cells, are changing The TreaTmenT paradigm for ALL. Tisagenlecleucel (kymriah, NovarTis) is an auTologous CD19-TargeTed CAR T cell producT approved for TreaTmenT of R/R B cell ALL and lymphoma. In an aTTempT To reduce The relapse raTe and TreaT Those relapsed paTienTs wiTh anTigen loss, donor-derived CAR T Cells and CD19/CD22 dual-TargeT CAR T Cells are in clinical Trials. Gene-ediTed “off-The-shelf” universal CAR T Cells are also undergoing acTive clinical developmenT. This review summarized new clinical Trials and laTesT updaTes aT The 2018 ASH Annual MeeTing on CAR T Therapy for ALL wiTh a focus on dual-TargeT CAR T and universal CAR T cell Trials

  • Universal CARs, universal T Cells, and universal CAR T Cells
    Journal of Hematology & Oncology, 2018
    Co-Authors: Juanjuan Zhao, Yongping Song
    Abstract:

    CurrenTly, The Two approved T cell producTs wiTh chimeric anTigen recepTors (CAR) are from auTologous T Cells. These CAR T Cells approved for clinical use musT be generaTed on a cusTom-made basis. This case-by-case auTologous T cell producTion plaTform remains a significanT limiTing facTor for large-scale clinical applicaTion due To The cosTly and lengThy producTion process. There is also an inherenT risk of producTion failure. The individualized, cusTom-made auTologous CAR T cell producTion process also posTs consTricTion on The wide applicaTion on diverse Tumor Types. Therefore, universal allogeneic T Cells are needed for The preparaTion of universal CAR T Cells ThaT can serve as The “off-The-shelf” ready-To-use TherapeuTic agenTs for large-scale clinical applicaTions. Genome-ediTing Technologies including ZFN (zinc finger nuclease), TALEN (TranscripTion acTivaTor-like effecTor nuclease), and CRISPR-Cas9 are being used To generaTe The universal Third-parTy T Cells. In addiTion, spliT, universal, and programmable (SUPRA) CARs are being developed To enhance The flexibiliTy and conTrollabiliTy of CAR T Cells. The engineered universal T Cells and universal CARs are paving The road for a ToTally new generaTion of CAR T Cells capable of TargeTing mulTiple anTigens and/ or being delivered To mulTiple recipienTs wiThouT re-ediTing of T Cells. This may escalaTe To a new wave of revoluTion in cancer immunoTherapy. This review summarized The laTesT advances on designs and developmenT of universal CARs, universal T Cells, and clinical applicaTion of universal CAR T Cells.

Mahmoud Abdelrasoul - One of the best experts on this subject based on the ideXlab platform.

  • anTibody suppressor cd8 T Cells require cxcr5
    Transplantation, 2019
    Co-Authors: Jason M Zimmerer, Bryce A Ringwald, Steven M Elzein, Christina L Avila, Robert T Warren, Mahmoud Abdelrasoul, Ginny L. Bumgardner
    Abstract:

    BACKGROUND We previously reporTed The novel acTiviTy of alloprimed CD8 T Cells ThaT suppress posTTransplanT alloanTibody producTion. The purpose of The sTudy is To invesTigaTe The expression and role of CXCR5 on anTibody-suppressor CD8 T-cell funcTion. METHODS C57BL/6 mice were TransplanTed wiTh FVB/N hepaTocyTes. Alloprimed CD8 T Cells were reTrieved on day 7 from hepaTocyTe TransplanT recipienTs. UnsorTed or flow-sorTed (CXCR5CXCR3 and CXCR3CXCR5) alloprimed CD8 T-cell subseTs were analyzed for in viTro cyToToxiciTy and capaciTy To inhibiT in vivo alloanTibody producTion following adopTive Transfer inTo C57BL/6 or high alloanTibody-producing CD8 knock ouT (KO) hepaTocyTe TransplanT recipienTs. AlloanTibody TiTer was assessed in CD8 KO mice reconsTiTuTed wiTh naive CD8 T Cells reTrieved from C57BL/6, CXCR5 KO, or CXCR3 KO mice. AnTibody suppression by ovalbumin (OVA)-primed monoclonal OVA-specific T-cell recepTor Transgenic CD8+ T Cells (OT-I) CXCR5 or CXCR3 CD8 T-cell subseTs was also invesTigaTed. RESULTS Alloprimed CXCR5CXCR3CD8 T Cells mediaTed in viTro cyToToxiciTy of alloprimed "self" B Cells, while CXCR3CXCR5CD8 T Cells did noT. Only flow-sorTed alloprimed CXCR5CXCR3CD8 T Cells (noT flow-sorTed alloprimed CXCR3CXCR5CD8 T Cells) suppressed alloanTibody producTion and enhanced grafT survival when Transferred inTo TransplanT recipienTs. Unlike CD8 T Cells from wild-Type or CXCR3 KO mice, CD8 T Cells from CXCR5 KO mice do noT develop alloanTibody-suppressor funcTion. Similarly, only flow-sorTed CXCR5CXCR3 (and noT CXCR3CXCR5) OVA-primed OT-I CD8 T Cells mediaTed in vivo suppression of anTi-OVA anTibody producTion. CONCLUSIONS These daTa supporT The conclusion ThaT expression of CXCR5 by anTigen-primed CD8 T Cells is criTical for The funcTion of anTibody-suppressor CD8 T Cells.

  • anTibody suppressor cd8 T Cells require cxcr5
    Transplantation, 2019
    Co-Authors: Jason M Zimmerer, Bryce A Ringwald, Steven M Elzein, Christina L Avila, Robert T Warren, Mahmoud Abdelrasoul, Ginny L. Bumgardner
    Abstract:

    BACKGROUND We previously reporTed The novel acTiviTy of alloprimed CD8 T Cells ThaT suppress posTTransplanT alloanTibody producTion. The purpose of The sTudy is To invesTigaTe The expression and role of CXCR5 on anTibody-suppressor CD8 T-cell funcTion. METHODS C57BL/6 mice were TransplanTed wiTh FVB/N hepaTocyTes. Alloprimed CD8 T Cells were reTrieved on day 7 from hepaTocyTe TransplanT recipienTs. UnsorTed or flow-sorTed (CXCR5CXCR3 and CXCR3CXCR5) alloprimed CD8 T-cell subseTs were analyzed for in viTro cyToToxiciTy and capaciTy To inhibiT in vivo alloanTibody producTion following adopTive Transfer inTo C57BL/6 or high alloanTibody-producing CD8 knock ouT (KO) hepaTocyTe TransplanT recipienTs. AlloanTibody TiTer was assessed in CD8 KO mice reconsTiTuTed wiTh naive CD8 T Cells reTrieved from C57BL/6, CXCR5 KO, or CXCR3 KO mice. AnTibody suppression by ovalbumin (OVA)-primed monoclonal OVA-specific T-cell recepTor Transgenic CD8+ T Cells (OT-I) CXCR5 or CXCR3 CD8 T-cell subseTs was also invesTigaTed. RESULTS Alloprimed CXCR5CXCR3CD8 T Cells mediaTed in viTro cyToToxiciTy of alloprimed "self" B Cells, while CXCR3CXCR5CD8 T Cells did noT. Only flow-sorTed alloprimed CXCR5CXCR3CD8 T Cells (noT flow-sorTed alloprimed CXCR3CXCR5CD8 T Cells) suppressed alloanTibody producTion and enhanced grafT survival when Transferred inTo TransplanT recipienTs. Unlike CD8 T Cells from wild-Type or CXCR3 KO mice, CD8 T Cells from CXCR5 KO mice do noT develop alloanTibody-suppressor funcTion. Similarly, only flow-sorTed CXCR5CXCR3 (and noT CXCR3CXCR5) OVA-primed OT-I CD8 T Cells mediaTed in vivo suppression of anTi-OVA anTibody producTion. CONCLUSIONS These daTa supporT The conclusion ThaT expression of CXCR5 by anTigen-primed CD8 T Cells is criTical for The funcTion of anTibody-suppressor CD8 T Cells.

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