The Experts below are selected from a list of 166893 Experts worldwide ranked by ideXlab platform

N Manjunath - One of the best experts on this subject based on the ideXlab platform.

  • CD70^+ Antigen-presenting cells control the proliferation and differentiation of T cells in the intestinal mucosa
    Nature Immunology, 2005
    Co-Authors: Amale Laouar, Viraga Haridas, Dorothy Vargas, Xia Zhinan, David Chaplin, Rene A W Van Lier, N Manjunath
    Abstract:

    One unresolved issue in gut immunity is how mucosal T lymphocytes are activated and which Antigen-presenting cell (APC) is critical for the regulation of this process. We have identified a unique population of APCs that is exclusively localized in the lamina propria. These APCs constitutively expressed the costimulatory molecule CD70 and had Antigen-presenting functions. After oral infection of mice with Listeria monocytogenes , proliferation and differentiation of Antigen-specific T cells occurred in the gut mucosa in situ and blockade of CD70 costimulation abrogated the mucosal T cell proliferation and effector functions. Thus, a potent CD70-dependent stimulation via specialized tissue-specific APCs is required for the proliferation and differentiation of gut mucosal T cells after oral infection.

Amale Laouar - One of the best experts on this subject based on the ideXlab platform.

  • CD70^+ Antigen-presenting cells control the proliferation and differentiation of T cells in the intestinal mucosa
    Nature Immunology, 2005
    Co-Authors: Amale Laouar, Viraga Haridas, Dorothy Vargas, Xia Zhinan, David Chaplin, Rene A W Van Lier, N Manjunath
    Abstract:

    One unresolved issue in gut immunity is how mucosal T lymphocytes are activated and which Antigen-presenting cell (APC) is critical for the regulation of this process. We have identified a unique population of APCs that is exclusively localized in the lamina propria. These APCs constitutively expressed the costimulatory molecule CD70 and had Antigen-presenting functions. After oral infection of mice with Listeria monocytogenes , proliferation and differentiation of Antigen-specific T cells occurred in the gut mucosa in situ and blockade of CD70 costimulation abrogated the mucosal T cell proliferation and effector functions. Thus, a potent CD70-dependent stimulation via specialized tissue-specific APCs is required for the proliferation and differentiation of gut mucosal T cells after oral infection.

Mary Lee Dequeant - One of the best experts on this subject based on the ideXlab platform.

  • Abstract 6595: Targeting T cell lymphomas with CRISPR/Cas9-generated anti-CD70 allogeneic CAR-T cells
    Immunology, 2020
    Co-Authors: Sushant Karnik, Zinkal Padalia, Minh Thu Pham, Pooja Keerthipati, Julie Carson, Ewelina Morawa, Matthias Will, Jonathan Alexander Terrett, Mary Lee Dequeant
    Abstract:

    T cell lymphomas account for 10% to 15% of non-Hodgkin lymphomas and are diverse biologically and clinically. Unlike B-cell lymphomas, T cell lymphomas are rather resistant to conventional therapies, such as chemotherapy and antibody-based therapeutics. This resistance coupled with the diversity of the T cell diseases means that there is a significant unmet need across the T cell lymphoma subtypes. CD70 (CD27 ligand) is a candidate target Antigen for T cell lymphomas and has been is the subject of clinical trials using an enhanced ADCC antibody (ARGX-110). Using flow cytometry and immunohistochemistry (IHC) methods, we analyzed the expression of CD70 in cell lines and clinical samples representing T cell lymphomas and found significant expression of CD70 in multiple types of T cell lymphoma, but at highly variable Antigen density. CAR-T cells targeting CD70 may thus be a potent new therapy to tackle these diseases. However, the use of autologous CAR-T therapy against T cell lymphomas is complicated by the likelihood of creating lymphoma cells carrying the CAR construct. Thus, we sought to examine the potency of our allogeneic anti-CD70 CAR-T cells (CTX130) against T cell lymphoma cells. CTX130 has previously been shown to be active across a range of CD70 expression levels in other cell types representing other malignancies. Consistent with these prior observations, CTX130 exhibited high potency in vitro and in vivo against T cell lymphoma cells across a range of CD70 Antigen density and representing different types of T cell lymphomas such as Sezary syndrome and cutaneous T cell lymphoma (CTCL). CTX130 may thus be a valid therapeutic to evaluate in T cell lymphoma patients. Citation Format: Sushant Karnik, Minh Thu Pham, Pooja Keerthipati, Zinkal Padalia, Julie Carson, Tony Ho, Ewelina Morawa, Matthias Will, Jonathan Terrett, Mary-Lee Dequeant. Targeting T cell lymphomas with CRISPR/Cas9-generated anti-CD70 allogeneic CAR-T cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6595.

  • Abstract 2551: Allogeneic CRISPR engineered anti CD70 CAR T cells demonstrate potent preclinical activity against both solid and hematological cancer cells
    Immunology, 2018
    Co-Authors: Zinkal Padalia, Ashley Porras, Mary Lee Dequeant, Jason Gary Sagert, Thao Nguyen, Matthias John, Melanie Allen, Henia Dar, Daniel R. Henderson
    Abstract:

    Autologous CAR T therapeutics have recently been approved for use in B-cell malignancies. While responses have been impressive using CD19 directed CAR T cells there has been a lack of comparable success for CAR T cells directed at solid tumor Antigens. In an effort to address the need for effective and durable off-the shelf therapies for both hematologic and solid tumors we have developed allogeneic CAR T cells targeting the CD70 Antigen. CD70 is expressed in both hematologic malignancies as well as in solid cancers such as renal cell carcinoma (RCC), while its expression in normal tissues is restricted to a subset of lymphoid cell types. CAR-T cells expressing a CD70 targeting CAR were generated by CRISPR Cas9 genome editing. T cells from healthy donors were edited to express a CD70 CAR by knocking this construct into the concurrently knocked out TCR alpha constant region (TRAC). Loss of the TCR reduces the risk of graft versus host disease enabling an allogeneic therapeutic. CD70 CAR T cells displayed potent cell killing function in vitro against CD70 expressing lymphoid and renal cancer derived cell lines across a broad range of Antigen expression levels. CD70 CAR T cells also secreted IFNg, released granzyme B and proliferated in a CD70 specific manner. Furthermore, the CD70 targeting CAR T cells were able to eliminate established ccRCC tumor xenografts in mice Citation Format: Zinkal Padalia, Ashley Porras, Mary Lee Dequeant, Jason Sagert, Thao Nguyen, Matthias John, Melanie Allen, Henia Dar, Daniel Henderson, Seshidar Police, Dakai Mu, Kelly Maeng, Elaine Huang, Sarah Spencer, Nickolaus Lorson, Paul Gonzales, Chelsea Holmquist, Gregg Hirschfeld, Jonathan A. Terrett, Demetrios Kalaitzidis. Allogeneic CRISPR engineered anti CD70 CAR T cells demonstrate potent preclinical activity against both solid and hematological cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2551.

Zinkal Padalia - One of the best experts on this subject based on the ideXlab platform.

  • Abstract 6595: Targeting T cell lymphomas with CRISPR/Cas9-generated anti-CD70 allogeneic CAR-T cells
    Immunology, 2020
    Co-Authors: Sushant Karnik, Zinkal Padalia, Minh Thu Pham, Pooja Keerthipati, Julie Carson, Ewelina Morawa, Matthias Will, Jonathan Alexander Terrett, Mary Lee Dequeant
    Abstract:

    T cell lymphomas account for 10% to 15% of non-Hodgkin lymphomas and are diverse biologically and clinically. Unlike B-cell lymphomas, T cell lymphomas are rather resistant to conventional therapies, such as chemotherapy and antibody-based therapeutics. This resistance coupled with the diversity of the T cell diseases means that there is a significant unmet need across the T cell lymphoma subtypes. CD70 (CD27 ligand) is a candidate target Antigen for T cell lymphomas and has been is the subject of clinical trials using an enhanced ADCC antibody (ARGX-110). Using flow cytometry and immunohistochemistry (IHC) methods, we analyzed the expression of CD70 in cell lines and clinical samples representing T cell lymphomas and found significant expression of CD70 in multiple types of T cell lymphoma, but at highly variable Antigen density. CAR-T cells targeting CD70 may thus be a potent new therapy to tackle these diseases. However, the use of autologous CAR-T therapy against T cell lymphomas is complicated by the likelihood of creating lymphoma cells carrying the CAR construct. Thus, we sought to examine the potency of our allogeneic anti-CD70 CAR-T cells (CTX130) against T cell lymphoma cells. CTX130 has previously been shown to be active across a range of CD70 expression levels in other cell types representing other malignancies. Consistent with these prior observations, CTX130 exhibited high potency in vitro and in vivo against T cell lymphoma cells across a range of CD70 Antigen density and representing different types of T cell lymphomas such as Sezary syndrome and cutaneous T cell lymphoma (CTCL). CTX130 may thus be a valid therapeutic to evaluate in T cell lymphoma patients. Citation Format: Sushant Karnik, Minh Thu Pham, Pooja Keerthipati, Zinkal Padalia, Julie Carson, Tony Ho, Ewelina Morawa, Matthias Will, Jonathan Terrett, Mary-Lee Dequeant. Targeting T cell lymphomas with CRISPR/Cas9-generated anti-CD70 allogeneic CAR-T cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6595.

  • Abstract 2551: Allogeneic CRISPR engineered anti CD70 CAR T cells demonstrate potent preclinical activity against both solid and hematological cancer cells
    Immunology, 2018
    Co-Authors: Zinkal Padalia, Ashley Porras, Mary Lee Dequeant, Jason Gary Sagert, Thao Nguyen, Matthias John, Melanie Allen, Henia Dar, Daniel R. Henderson
    Abstract:

    Autologous CAR T therapeutics have recently been approved for use in B-cell malignancies. While responses have been impressive using CD19 directed CAR T cells there has been a lack of comparable success for CAR T cells directed at solid tumor Antigens. In an effort to address the need for effective and durable off-the shelf therapies for both hematologic and solid tumors we have developed allogeneic CAR T cells targeting the CD70 Antigen. CD70 is expressed in both hematologic malignancies as well as in solid cancers such as renal cell carcinoma (RCC), while its expression in normal tissues is restricted to a subset of lymphoid cell types. CAR-T cells expressing a CD70 targeting CAR were generated by CRISPR Cas9 genome editing. T cells from healthy donors were edited to express a CD70 CAR by knocking this construct into the concurrently knocked out TCR alpha constant region (TRAC). Loss of the TCR reduces the risk of graft versus host disease enabling an allogeneic therapeutic. CD70 CAR T cells displayed potent cell killing function in vitro against CD70 expressing lymphoid and renal cancer derived cell lines across a broad range of Antigen expression levels. CD70 CAR T cells also secreted IFNg, released granzyme B and proliferated in a CD70 specific manner. Furthermore, the CD70 targeting CAR T cells were able to eliminate established ccRCC tumor xenografts in mice Citation Format: Zinkal Padalia, Ashley Porras, Mary Lee Dequeant, Jason Sagert, Thao Nguyen, Matthias John, Melanie Allen, Henia Dar, Daniel Henderson, Seshidar Police, Dakai Mu, Kelly Maeng, Elaine Huang, Sarah Spencer, Nickolaus Lorson, Paul Gonzales, Chelsea Holmquist, Gregg Hirschfeld, Jonathan A. Terrett, Demetrios Kalaitzidis. Allogeneic CRISPR engineered anti CD70 CAR T cells demonstrate potent preclinical activity against both solid and hematological cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2551.

Dorothy Vargas - One of the best experts on this subject based on the ideXlab platform.

  • CD70^+ Antigen-presenting cells control the proliferation and differentiation of T cells in the intestinal mucosa
    Nature Immunology, 2005
    Co-Authors: Amale Laouar, Viraga Haridas, Dorothy Vargas, Xia Zhinan, David Chaplin, Rene A W Van Lier, N Manjunath
    Abstract:

    One unresolved issue in gut immunity is how mucosal T lymphocytes are activated and which Antigen-presenting cell (APC) is critical for the regulation of this process. We have identified a unique population of APCs that is exclusively localized in the lamina propria. These APCs constitutively expressed the costimulatory molecule CD70 and had Antigen-presenting functions. After oral infection of mice with Listeria monocytogenes , proliferation and differentiation of Antigen-specific T cells occurred in the gut mucosa in situ and blockade of CD70 costimulation abrogated the mucosal T cell proliferation and effector functions. Thus, a potent CD70-dependent stimulation via specialized tissue-specific APCs is required for the proliferation and differentiation of gut mucosal T cells after oral infection.