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Articles by Mark Leick
Selecting Donor T Cells for CAR T Therapy, With Mark B. Leick, MD
Findings from a germline genetics study of CAR T cell therapy could help guide how researchers select donor T cells for allogeneic, "off the shelf" CAR T products. The results also point to a new way to identify genes that could improve future CAR T cell designs. Mark B.
A Genetic Signature May Predict Who Gets Sick From CAR T Cell Therapy
Published on: Germline STXBP2 variants may predict severe CAR T cell toxicity, Mark B.
Germline Variants May Predict CAR T Cell Toxicity, With Mark Leick, MD
Published on: New research links germline genetic variants to CAR T cell toxicity risk and expansion in lymphoma patients treated with axi-cel.
Genomic correlates of clinical CAR T cell activity
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Editor’s summary Abstract INTRODUCTION RESULTS DISCUSSION MATERIALS AND METHODS Acknowledgments Supplementary Materials REFERENCES AND NOTES Information & Authors Metrics & Citations View Options References Figures Tables Media Share Editor’s summary Chimeric antigen receptor T cell (CAR T cell) therapies are generated from human T cells and carry germline variants that may affect their function. Leick et al.
By WeiWei Yu, Mark Leick, Maria Pia Holgado, Baihe Sun, Filippo Birocchi, Kathleen Gallagher Verified, Seunghun Han, Grace Martin, Harrison Silva, Rebecca Larson, Tyler M. Chinsky, Hoyin Chu, Christopher Reilly, Michael Kann, Bryan D. Choi, Sabrina Y. Camp, Riaz Gillani, Merle K. Phillips, Tamina Kienka, Stefanie R Bailey, Charlotte Graham, Max Jan, Nicholas Moore, Nora K. Horick, Alexandra Bratt
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Science Magazine
Verified
Dynamic regulation of lysine and arginine metabolism promotes immune evasion by limiting T cell function in cancer
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Editor’s summary Abstract Supplementary Materials REFERENCES AND NOTES Information & Authors Metrics & Citations Check Access References Figures Tables Media Share Editor’s summary Metabolic adaptations alter the tumor microenvironment, but the impact on tumor progression and antitumor immunity remains unclear. Yu et al. revealed that lysine and arginine metabolism were dynamically altered with tumor progression across mouse tumor models and patient datasets.
By WeiWei Yu, Mark Leick, Maria Pia Holgado, Ruya Sun, Xiaoyang Lu, Qiqi Deng, Heng Zhang, Sheng Chen, Siqi Dai, TianYi Hu, Xiangyuan Li, Yidong Yang, Lihao Chen, Zhexu Chi, Jian Zhang, Siwen Zhang, Yiyi Zhu, Dehang Yang, Qianzhou Yu, Zhen Wang, Quanquan Wang, Fan Yang, Qian Xiao, Kefeng Ding, Di Wang
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Science Magazine
Verified
Tuning CAR-T cells by targeting cancer-associated glycan in pancreatic cancer - Nature Communications
Abstract Chimeric antigen receptor (CAR) T cell therapy has transformed cancer treatment but its efficacy remains limited in solid tumors due to antigen heterogeneity, an immunosuppressive microenvironment, and the glycocalyx barrier. The glycocalyx, composed of dense glycoproteins such as MUC1, is markedly expanded in cancers, where it impedes immune cell access and antigen engagement, thereby reducing efficacy.
On-target off-tumor toxicity of claudin18.2-directed CAR-T cells in preclinical models - Nature Communications
Abstract Claudin 18.2 (CLDN18.2)-targeted CAR-T cell therapies have shown promising clinical efficacy in gastric cancer. However, early-phase trials have reported gastrointestinal adverse events due to on-target off-tumor recognition of CLDN18.2 in the gastric mucosa. By leveraging shared CLDN18.2 epitopes and expression in humans and mice, we establish an in vivo model that replicates the on-target off-tumor toxicity of CLDN18.2 CAR-T.
In vivo CRISPR screens identify modifiers of CAR T cell function in myeloma - Nature
Abstract Chimeric antigen receptor (CAR) T cells are highly effective in haematological malignancies1. However, progressive loss of CAR T cells contributes to relapse in many patients2,3,4. Here we performed in vivo loss-of-function CRISPR screens in CAR T cells targeting B cell maturation antigen to investigate genes that influence CAR T cell persistence and function in a human multiple myeloma model.
Comparative analysis of Bcl-2 family protein overexpression in CAR T cells alone and in combination with BH3 mimetics
Research Article CANCER Felix Korell https://orcid.org/0000-0001-7699-7212, Michael L. Olson https://orcid.org/0000-0002-1566-2029, [...] , Diego Salas-Benito https://orcid.org/0000-0002-8995-1499, Mark B. Leick https://orcid.org/0000-0003-3111-0221, [...] , Rebecca C. Larson https://orcid.org/0000-0003-0174-061X, Amanda Bouffard, Harrison Silva https://orcid.org/0000-0003-4386-0847, Alessandro Gasparetto https://orcid.org/0000-0003-1665-3594, Trisha R.
Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma | NEJM
Notes This article was published on March 13, 2024, at NEJM.org. A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.
Chemical genetic control of cytokine signaling in CAR-T cells using lenalidomide-controlled membrane-bound degradable IL-7 - Leukemia
Abstract CAR-T cell therapy has emerged as a breakthrough therapy for the treatment of relapsed and refractory hematologic malignancies. However, insufficient CAR-T cell expansion and persistence is a leading cause of treatment failure. Exogenous or transgenic cytokines have great potential to enhance CAR-T cell potency but pose the risk of exacerbating toxicities.
Low incidence of engraftment syndrome following allogeneic hematopoietic cell transplantation with post-transplant cyclophosphamide - Bone Marrow Transplantation
This is a preview of subscription content, access via your institution Access options Subscribe to this journal Receive 12 print issues and online access $259.00 per year only $21.58 per issue Rent or buy this article Prices vary by article type from$1.95 to$39.95 Prices may be subject to local taxes which are calculated during checkout References Luznik L, O’Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, et al.
Non-cleavable hinge enhances avidity and expansion of CAR-T cells for acute myeloid leukemia
Abramson J.S. Palomba M.L. Gordon L.I. Lunning M.A. Wang M. Arnason J. Mehta A. Purev E. Maloney D.G. Andreadis C. et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020; 396: 839-852https://doi.org/10.1016/S0140-6736(20)31366-0 Actavis_Pharma, S.P.S. Azacitidine [package Insert]. U.S. Food and Drug Administration Alabanza L. Pegues M. Geldres C. Shi V. Wiltzius J.J.W. Sievers S.A. Yang S.
Telephone | NEJM
2 References Related Articles Article As a child, you probably played the game “Telephone”: you whispered a message into the ear of the person next to you, who whispered it to the next person, and so forth down the line. When revealed at the end of the chain, the message was inevitably garbled, illustrating how fragile human communication can be. For children, these mistranslations were hilarious.
Tisagenlecleucel CAR T-cell therapy in secondary CNS lymphoma
Matthew J. Frigault, Jorg Dietrich, Maria Martinez-Lage, Mark Leick, Bryan D. Choi, Zachariah DeFilipp, Yi-Bin Chen, Jeremy Abramson, Jennifer Crombie, Philippe Armand, Lakshmi Nayak, Chris Panzini, Lauren S. Riley, Kathleen Gallagher and Marcela V. Maus Blood 2019 134:860-866; doi: https://doi.org/10.1182/blood.2019001694 Key Points Tisagenlecleucel for secondary CNS lymphoma has an acceptable safety profile.
Tisagenlecleucel CAR-T Cell Therapy in Secondary CNS Lymphoma
Matthew J. Frigault, Jorg Dietrich, Maria Martinez-Lage, Mark Leick, Bryan D. Choi, Zachariah DeFilipp, Yi-Bin Chen, Jeremy Abramson, Jennifer Crombie, Philippe Armand, Lakshmi Nayak, Christopher Panzini, Lauren S. Riley, Kathleen Gallagher and Marcela Maus Blood 2019 :blood.2019001694; doi: https://doi.org/10.1182/blood.2019001694 Key Points Tisagenlecleucel for secondary CNS lymphoma has an acceptable safety profile.
Wishing on a CAR: Understanding the Scope of Intrinsic T-cell Deficits in Patients with Cancer
In the Spotlight Mark Leick and Marcela V. Maus DOI: 10.1158/2159-8290.CD-19-0073 Published April 2019 Abstract Summary: Treatment with chimeric antigen receptor T cells has led to impressive and durable responses in adult and pediatric malignancies refractory to conventional therapy; however, only patients with a handful of cancers have responded thus far and significant disparities exist between the response rates of pediatric and adult patients.
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