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Understanding the Mechanisms of Resistance in CAR T Immunotherapy for Lymphoma and Strategies to...
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Presented By: Marco Ruella
Speaker Biography:
I am a tenure-track Assistant Professor of Medicine at the University of Pennsylvania and the Scientific Director of the Lymphoma Program at the Hospital of the University of Pennsylvania. As a physician-scientist, my overall goal is to run a research program to improve the outcome of patients with relapsed or refractory hematologic malignancies. I have acquired significant expertise in studying the mechanisms of relapse after targeted immunotherapies and developing successful chimeric antigen receptor T cells (CART) for patients with lymphoid malignancies (see citations below). Several projects that I led have significantly contributed to the advancement of the field by providing: i. a better understanding of the mechanisms of resistance in patients treated with CART19 (role of apoptosis; epitope-masking; antigen-negative escape); ii. first-in-human innovative clinical trials (CART19+ibrutinib, anti-CD19/CD22 CART). Our ultimate research objective is to improve CART therapy for cancer by studying tumor evasion mechanisms and rationally designing novel CART approaches.
Ongoing and recently completed projects that I would like to highlight include:
R01/R37 R01CA262362; Ruella (PI) 4/1/2022-3/31/2029; Modulation of cd5 signaling to enhance adoptive T-cell therapies for cancer
Hairy Cell Leukemia Foundation-Leukemia & Lymphoma Society HCL2025 Initiative Translational Grant; Ruella (PI); 9/1/22-8/31/25; Precision Targeting of Hairy Cell Leukemia using CAR T cells
K99 1K99CA212302-01A1; Ruella (PI); 06/02/2017-05/31/18 and R00 R00CA212302; Ruella (PI); 09/12/2018-06/30/21 Resistance To Targeted Immunotherapies: CART19 as a Paradigm
Webinar: Understanding the Mechanisms of Resistance in CAR T Immunotherapy for Lymphoma and Strategies to Overcome Them
Webinar Abstract:
In the past 5 years, the US Food and Drug Administration has approved 4 anti-CD19 chimeric antigen receptor T cell (CAR T19) products for relapsed/refractory B cell lymphomas and leukemia. However, we and others showed that only ~30-40% of patients maintain a durable complete remission at long term. Several interrelated factors contribute to the lack of response or relapse after CAR T19, including tumor cell-intrinsic factors, CAR T cell dysfunction, and an immunosuppressive tumor microenvironment (TME). Therefore, our goal is to develop next-generation immunotherapies that are characterized by enhanced cytotoxicity against lymphoma and leukemia cells in the complex dynamic of the immunosuppressive TME and with an acceptable safety profile.
We run a research program aimed to improve the outcome of patients with relapsed or refractory hematologic malignancies. We have acquired significant expertise in studying the mechanisms of relapse after targeted immunotherapies and developing successful chimeric antigen receptor T cells (CAR T) for patients with lymphoid malignancies. Several projects that we led have significantly contributed to the advancement of the field by providing: i. a better understanding of the mechanisms of resistance in patients treated with CAR T19 (role of apoptosis; epitope-masking; antigen-negative escape); ii. first-in-human innovative clinical trials (CAR T19+ibrutinib, anti-CD19/CD22 CAR T).
Our lab uses a combination of next-generation techniques (scRNA sequencing, spatial transcriptomic, etc.) to characterize mechanisms of resistance, perform pre-clinical studies, and develop new CAR T products. Our ultimate research objective is to improve CAR T therapy for cancer by studying tumor evasion mechanisms and rationally designing novel CAR T approaches.
In this presentation, we'll describe some of our recent findings on resistance mechanisms to CAR T cells, focusing on cell-intrinsic factors and CAR T cell dysfunction. We'll also discuss other limitations of CAR T immunotherapy and propose possible strategies to overcome them.
Learning Objectives:
Why are CAR T very successful in the clinic, but why do most patients relapse? Moreover, why do a significant subset of them experience severe toxicity?
Multiple mechanisms of relapse have been identified. Learn about T-cell dysfunction, the tumor microenvironment, and tumor intrinsic resistance
What novel approaches have been developed to reduce toxicity and to enhance efficacy?
Labroots on Social:
SnapChat: labroots_inc
Speaker Biography:
I am a tenure-track Assistant Professor of Medicine at the University of Pennsylvania and the Scientific Director of the Lymphoma Program at the Hospital of the University of Pennsylvania. As a physician-scientist, my overall goal is to run a research program to improve the outcome of patients with relapsed or refractory hematologic malignancies. I have acquired significant expertise in studying the mechanisms of relapse after targeted immunotherapies and developing successful chimeric antigen receptor T cells (CART) for patients with lymphoid malignancies (see citations below). Several projects that I led have significantly contributed to the advancement of the field by providing: i. a better understanding of the mechanisms of resistance in patients treated with CART19 (role of apoptosis; epitope-masking; antigen-negative escape); ii. first-in-human innovative clinical trials (CART19+ibrutinib, anti-CD19/CD22 CART). Our ultimate research objective is to improve CART therapy for cancer by studying tumor evasion mechanisms and rationally designing novel CART approaches.
Ongoing and recently completed projects that I would like to highlight include:
R01/R37 R01CA262362; Ruella (PI) 4/1/2022-3/31/2029; Modulation of cd5 signaling to enhance adoptive T-cell therapies for cancer
Hairy Cell Leukemia Foundation-Leukemia & Lymphoma Society HCL2025 Initiative Translational Grant; Ruella (PI); 9/1/22-8/31/25; Precision Targeting of Hairy Cell Leukemia using CAR T cells
K99 1K99CA212302-01A1; Ruella (PI); 06/02/2017-05/31/18 and R00 R00CA212302; Ruella (PI); 09/12/2018-06/30/21 Resistance To Targeted Immunotherapies: CART19 as a Paradigm
Webinar: Understanding the Mechanisms of Resistance in CAR T Immunotherapy for Lymphoma and Strategies to Overcome Them
Webinar Abstract:
In the past 5 years, the US Food and Drug Administration has approved 4 anti-CD19 chimeric antigen receptor T cell (CAR T19) products for relapsed/refractory B cell lymphomas and leukemia. However, we and others showed that only ~30-40% of patients maintain a durable complete remission at long term. Several interrelated factors contribute to the lack of response or relapse after CAR T19, including tumor cell-intrinsic factors, CAR T cell dysfunction, and an immunosuppressive tumor microenvironment (TME). Therefore, our goal is to develop next-generation immunotherapies that are characterized by enhanced cytotoxicity against lymphoma and leukemia cells in the complex dynamic of the immunosuppressive TME and with an acceptable safety profile.
We run a research program aimed to improve the outcome of patients with relapsed or refractory hematologic malignancies. We have acquired significant expertise in studying the mechanisms of relapse after targeted immunotherapies and developing successful chimeric antigen receptor T cells (CAR T) for patients with lymphoid malignancies. Several projects that we led have significantly contributed to the advancement of the field by providing: i. a better understanding of the mechanisms of resistance in patients treated with CAR T19 (role of apoptosis; epitope-masking; antigen-negative escape); ii. first-in-human innovative clinical trials (CAR T19+ibrutinib, anti-CD19/CD22 CAR T).
Our lab uses a combination of next-generation techniques (scRNA sequencing, spatial transcriptomic, etc.) to characterize mechanisms of resistance, perform pre-clinical studies, and develop new CAR T products. Our ultimate research objective is to improve CAR T therapy for cancer by studying tumor evasion mechanisms and rationally designing novel CAR T approaches.
In this presentation, we'll describe some of our recent findings on resistance mechanisms to CAR T cells, focusing on cell-intrinsic factors and CAR T cell dysfunction. We'll also discuss other limitations of CAR T immunotherapy and propose possible strategies to overcome them.
Learning Objectives:
Why are CAR T very successful in the clinic, but why do most patients relapse? Moreover, why do a significant subset of them experience severe toxicity?
Multiple mechanisms of relapse have been identified. Learn about T-cell dysfunction, the tumor microenvironment, and tumor intrinsic resistance
What novel approaches have been developed to reduce toxicity and to enhance efficacy?
Labroots on Social:
SnapChat: labroots_inc
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