ASH 2023: MRD Highlights in BioPharma Drug Development

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TCRseq Reveals Selected Donor-reactive CD8+ T cell Clones Resist Anti-Thymocyte Globulin Depletion after Kidney Transplantation

Ningoo M, et al.
American Journal of Transplantation
December 2023
Authors and Affiliates
Mehek Ningoo 1, Pamela Cruz-Encarnación 1, Calla Khilnani 1, Peter S Heeger 2, Miguel Fribourg 3; 1 Translational Transplant Research Center, Division of Nephrology, Department of Medicine; Immunology Institute Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 2 Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA. 3 Translational Transplant Research Center, Division of Nephrology, Department of Medicine; Immunology Institute Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: miguel.fribourg@mssm.edu.

The ERK inhibitor LY3214996 augments anti-PD-1 immunotherapy in preclinical mouse models of BRAFV600E melanoma brain metastasis

de Sauvage MA, at al.
neuro-oncology
December 2023
Authors and Affiliates
Magali A de Sauvage 1,2, Consuelo Torrini 1, Edwin Nieblas-Bedolla 1, Elizabeth Summers 1, Emily Sullivan 1, Britney S Zhang 1, Emily Batchelor 1, Braxton Marion 1, Erika Yamazawa 1, Samuel C Markson 3,4, Hiroaki Wakimoto 1, Naema Nayyar 1, Priscilla Brastianos 1,5; 1 Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA. 2 University of Utah School of Medicine, Salt Lake City, UT, USA. 3 Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. 4 Broad Institute of MIT and Harvard, Cambridge, MA, USA. 5 Division of Hematology/Oncology and Neuro-Oncology, Department of Medicine & Neurology, Massachusetts General Hospital. Boston, MA.

Identification of unstable regulatory and autoreactive effector T cells that are expanded in patients with FOXP3 mutations

Borna S, et al.
Science Translational Medicine
December 2023
Authors and Affiliates
Šimon Borna 1, Esmond Lee 1,2, Jason Nideffer 1, Akshaya Ramachandran 1, Bing Wang 1, Jeanette Baker 3, Melissa Mavers 1, Uma Lakshmanan 1, Mansi Narula 1, Amy Kang-Hee Garrett 1, Janika Schulze 4, Sven Olek 5, Louis Marois 6, Yael Gernez 7, Monica Bhatia 8, Hey Jin Chong 9, Jolan Walter 10, Maleewan Kitcharoensakkul 11, Abigail Lang 12,13, Megan A Cooper 14, Alice Bertaina 1,15, Maria Grazia Roncarolo 1,2,15, Eric Meffre 16, Rosa Bacchetta 1,15; 1 Department of Pediatrics, Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. 2 Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. 3 Department of Medicine, Division of Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA 94305, USA. 4 Epimune GmbH, Berlin 12489, Germany. 5 Ivana Turbachova Laboratory for Epigenetics, Precision for Medicine GmbH, Berlin 12489, Germany. 6 Department of Medicine, Immunology and Allergy Service, CHU de Québec-Laval University, Quebec G1V 4G2, Canada. 7 Department of Pediatrics, Division of Allergy, Rheumatology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. 8 Columbia University Irving Medical Center, New York, NY 10032, USA. 9 Division of Allergy and Immunology, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, USA. 10 Division of Allergy and Immunology, Department of Pediatrics, Johns Hopkins All Children's Hospital, University of South Florida, St. Petersburg, FL 33701, USA. 11 Divisions of Rheumatology/Immunology and Allergy and Pulmonary Medicine, Department of Pediatrics, Washington University in St. Louis, St. Louis, MO 63110, USA. 12 Department of Pediatrics, Division of Allergy and Immunology, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA. 13 Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. 14 Department of Pediatrics, Division of Rheumatology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA. 15 Center for Definitive and Curative Medicine (CDCM), Stanford University School of Medicine, Stanford, CA 94305, USA. 16 Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, 269 Campus Drive West, Stanford, CA 94305, USA.

Tracking DNA-based antigen-specific T cell receptors during progression to type 1 diabetes

Mitchell AM, et al.
Science Advances
December 2023
Authors and Affiliates
Angela M Mitchell 1, Erin E Baschal 1, Kristen A McDaniel 1, Theodore Fleury 1, Hyelin Choi 1, Laura Pyle 1,2, Liping Yu 1,3, Marian J Rewers 1,3,4, Maki Nakayama 1,3,5, Aaron W Michels 1,3,4,5; 1 Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA. 2 Department of Biostatistics and Informatics, University of Colorado School of Public Health, Aurora, CO, USA. 3 Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA. 4 Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA. 5 Department of Immunology, University of Colorado School of Medicine, Aurora, CO, USA.

LTX-315 and adoptive cell therapy using tumor-infiltrating lymphocytes generate tumor specific T cells in patients with metastatic soft tissue sarcoma

Nielsen M, et al.
OncoImmunology
December 2023
Authors and Affiliates
Morten Nielsen 1, Tine Monberg 1, Vibeke Sundvold 2, Benedetta Albieri 1, Dorrit Hovgaard 3, Michael Mørk Petersen 3, Anders Krarup-Hansen 4, Özcan Met 1 5, Ketil Camilio 2, Trevor Clancy 6, Richard Stratford 6, Baldur Sveinbjornsson 2, Øystein Rekdal 2, Niels Junker 4, Inge Marie Svane 1; 1 National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Herlev, Denmark. 2 Lytix Biopharma, Oslo, Norway. 3 Department of Orthopedic Surgery, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. 4 Department of Oncology, Herlev and Gentofte Hospital, Herlev, Denmark. 5 Department of Health Technology, Technical University of Denmark, Lyngby, Denmark. 6 NEC Oncoimmunity AS, Oslo, Norway.

Loss of function of XBP1 splicing activity of IRE1α favors B cell tolerance breakdown

Reuschle Q, et al.
Journal of Autoimmunity
December 2023
Authors and Affiliates
Quentin Reuschlé 1, Laurien Van Heddegem 2, Victor Bosteels 2, Matthieu Moncan 3, Sabine Depauw 4, Nadège Wadier 4, Sandra Maréchal 2, Clint De Nolf 5, Virginia Delgado 4, Yosra Messai 6, Marie-Claude Stolzenberg 3, Aude Magérus 3, Angélique Werck 7, Jérôme Olagne 8, Quan Li 9, Guillaume Lefevre 10, Anne-Sophie Korganow 11, Frédéric Rieux-Laucat 3, Sophie Janssens 2, Pauline Soulas-Sprauel 12; 1 Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM UMR_S1109, F-67000, Strasbourg, France; Strasbourg University, Faculty of Pharmacy and Faculty of Medicine, Strasbourg, France; Arthritis R&D, Neuilly sur Seine, France. 2 Laboratory for ER Stress and Inflammation, VIB Center for Inflammation Research, Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium. 3 Université Paris Cité, Laboratoire d'immunogénétique des maladies auto-immunes pédiatriques, Institut Imagine, INSERM UMR_S1163, Paris, France. 4 Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM UMR_S1109, F-67000, Strasbourg, France; Strasbourg University, Faculty of Pharmacy and Faculty of Medicine, Strasbourg, France. 5 Laboratory for ER Stress and Inflammation, VIB Center for Inflammation Research, Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium; Barriers in Inflammation, VIB Center for Inflammation Research, Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. 6 Arthritis R&D, Neuilly sur Seine, France. 7 Department of Pathology, University Hospital, Strasbourg, France. 8 Department of Pathology, University Hospital, Strasbourg, France; Department of Adult Nephrology, University Hospital, Strasbourg, France. 9 Department of Immunology, UT Southwestern Medical Center, Dallas, TX, USA. 10 Inserm, U1286 - INFINITE - Institute for Translational Research in Inflammation, University of Lille, CHU Lille, Lille, France. 11 Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM UMR_S1109, F-67000, Strasbourg, France; Strasbourg University, Faculty of Pharmacy and Faculty of Medicine, Strasbourg, France; Department of Clinical Immunology and Internal Medicine, National Reference Center for Systemic Autoimmune Diseases (CNR RESO), Tertiary Center for Primary Immunodeficiency, Strasbourg University Hospital, F-67000, Strasbourg, France. 12 Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM UMR_S1109, F-67000, Strasbourg, France; Strasbourg University, Faculty of Pharmacy and Faculty of Medicine, Strasbourg, France; Department of Clinical Immunology and Internal Medicine, National Reference Center for Systemic Autoimmune Diseases (CNR RESO), Tertiary Center for Primary Immunodeficiency, Strasbourg University Hospital, F-67000, Strasbourg, France. Electronic address: soulaspa@unistra.fr.

Safety and pharmacokinetics of imaradenant (AZD4635) in Japanese patients with advanced solid malignancies: a phase I, open-label study

Matsubara N, et al.
December 2023
Authors and Affiliates
Nobuaki Matsubara 1, Shota Kusuhara 2, Noboru Yamamoto 3, Kazuki Sudo 3, Masahiko Yanagita 4,5, Kosho Murayama 6, Hisashi Kawasumi 4, Deanna L Russell 7, Da Yin 8, Toshio Shimizu 3,9; 1 Department of Medical Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. nmatsuba@east.ncc.go.jp. 2 Department of Medical Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. 3 Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan. 4 Research & Development, AstraZeneca K.K., Tokyo, Japan. 5 Oncology Medical Affairs, Pfizer Japan Inc., Tokyo, Japan. 6 Research & Development, AstraZeneca K.K., Osaka, Japan. 7 Translational Medicine, Early Oncology, Oncology R&D, AstraZeneca Pharmaceuticals, Boston, MA, USA. 8 Oncology Data Science, Research and Early Development, Oncology R&D, AstraZeneca Pharmaceuticals, Gaithersburg, MD, USA. 9 Department of Pulmonary Medicine and Medical Oncology, Wakayama Medical University Graduate School of Medicine, Wakayama Medical University Hospital, Wakayama, Japan.

Plasticity of intragraft alloreactive T cell clones in human gut correlates with transplant outcomes

Fu J, et al.
Journal of Experimental Medicine
December 2023
Authors and Affiliates
Jianing Fu 1, Zicheng Wang 2, Mercedes Martinez 3, Aleksandar Obradovic 1, Wenyu Jiao 1, Kristjana Frangaj 1, Rebecca Jones 1, Xinzheng V Guo 4, Ya Zhang 4, Wan-I Kuo 4, Huaibin M Ko 5, Alina Iuga 5, Constanza Bay Muntnich 1, Adriana Prada Rey 1, Kortney Rogers 1, Julien Zuber 1, Wenji Ma 2, Michelle Miron 6, Donna L Farber 6,7, Joshua Weiner 1,7, Tomoaki Kato 7, Yufeng Shen 2, Megan Sykes 1,6,7; 1 Department of Medicine, Columbia Center for Translational Immunology, Columbia University, New York, NY, USA. 2Department of Systems Biology, Center for Computational Biology and Bioinformatics, Columbia University, New York, NY, USA. 3 Department of Pediatrics, Columbia University, New York, NY, USA. 4 Human Immune Monitoring Core, Herbert Irving Comprehensive Cancer Center, Columbia University , New York, NY, USA. 5 Department of Pathology and Cell Biology, Columbia University, New York, NY, USA. 6 Department of Microbiology and Immunology, Columbia University, New York, NY, USA. 7 Department of Surgery, Columbia University, New York, NY, USA.

Repeated mRNA vaccination sequentially boosts SARS-CoV-2-specific CD8+ T cells in persons with previous COVID-19

Ford ES, et al.
Nature Immunology
December 2023
Authors and Affiliates
Emily S Ford 1,2, Koshlan Mayer-Blackwell 2, Lichen Jing 1, Kerry J Laing 1, Anton M Sholukh 2, Russell St Germain 2, Emily L Bossard 2, Hong Xie 3, Thomas H Pulliam 1, Saumya Jani 1,3, Stacy Selke 3, Carlissa J Burrow 1, Christopher L McClurkan 1, Anna Wald 1,2,3,4, Alexander L Greninger 2,3, Michael R Holbrook 5, Brett Eaton 5, Elizabeth Eudy 5, Michael Murphy 5, Elena Postnikova 5, Harlan S Robins 6, Rebecca Elyanow 6, Rachel M Gittelman 6,7, Matyas Ecsedi 8,9, Elise Wilcox 8, Aude G Chapuis 1,8, Andrew Fiore-Gartland 2, David M Koelle 10,11,12,13,14; 1 Department of Medicine, University of Washington, Seattle, WA, USA. 2 Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. 3 Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA. 4 Department of Epidemiology, University of Washington, Seattle, WA, USA. 5 Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA. 6 Adaptive Biotechnologies, Seattle, WA, USA. 7 Guardant Health, Redwood City, CA, USA. 8 Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. 9 Takeda Oncology, Cambridge, MA, USA. 10 Department of Medicine, University of Washington, Seattle, WA, USA. 11 Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. 12 Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA. 13 Department of Global Health, University of Washington, Seattle, WA, USA. 14 Department of Translational Research, Benaroya Research Institute, Seattle, WA, USA. dkoelle@medicine.washington.edu.

Phenotypic signatures of circulating neoantigen-reactive CD8+ T cells in patients with metastatic cancers

Yossef R, et al.
Cancer Cell
December 2023
Authors and Affiliates
Rami Yossef 1, Sri Krishna 2, Sivasish Sindiri 3, Frank J Lowery 3, Amy R Copeland 3, Jared J Gartner 3, Maria R Parkhurst 3, Neilesh B Parikh 3, Kyle J Hitscherich 3, Shoshana T Levi 3, Praveen D Chatani 3, Nikolaos Zacharakis 3, Noam Levin 3, Nolan R Vale 3, Shirley K Nah 3, Aaron Dinerman 3, Victoria K Hill 3, Satyajit Ray 3, Alakesh Bera 3, Lior Levy 3, Li Jia 4, Michael C Kelly 5, Stephanie L Goff 3, Paul F Robbins 3, Steven A Rosenberg 6; 1 Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: yosef.rami@gmail.com. 2 Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: sri.krishna@nih.gov. 3 Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. 4 National Institutes of Health Library, National Institutes of Health, Bethesda, MD 20892, USA. 5 Single Cell Analysis Facility, Cancer Research Technology Program, Frederick National Laboratory, Bethesda, MD 20892, USA. 6 Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: sar@nih.gov.