CAR-T Cell–Mediated B-Cell Depletion in Central Nervous System Autoimmunity
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Article Information
- Received October 7, 2022
- Accepted in final form November 7, 2022
- First Published January 19, 2023.
Author Disclosures
- Sasha Gupta, MD,
- Milos Simic, PhD,
- Sharon A. Sagan, BS,
- Chanelle Shepherd, BS,
- Jason Duecker, BS,
- Raymond A. Sobel, MD,
- Ravi Dandekar, MS,
- Gregory F. Wu, MD, PhD,
- Wesley Wu, PhD,
- John E. Pak, PhD,
- Stephen L. Hauser, MD,
- Wendell Lim, PhD,
- Michael R. Wilson, MD* and
- Scott S. Zamvil, MD, PhD*
- Sasha Gupta, MD,
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I received funding from my fellowship from the National MS Society and Alpha-Stem Cell-CIRM foundation.
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- Milos Simic, PhD,
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None related to this work
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NMSS postodoctoral fellowship
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I have the following stocks::- VIR- MRNA- VBIV- INO- NVAX- REGN- SRNE- BNTX
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- Sharon A. Sagan, BS,
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- Chanelle Shepherd, BS,
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- Jason Duecker, BS,
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(1) Lyell Immunopharma, Research Associate II, 0.5
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(1) Lyell Immunopharma, 0.25
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- Raymond A. Sobel, MD,
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Journal of Neuropathology and Experimental Neurology, Deputy Editor, 2017-present,Journal of Neuroimmunology, Associate Editor, 2000-present
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NIH, R01 NS030843. VK Kuchroo, PI. Role: Co-Investigator, 2010– 2020. NIH, NS108159-01. SS Zamvil, PI. Role: Co-Investigator, 2018-2020 NIH. R01 AI131624. SS Zamvil, PI. Role: Co-Investigator, 2018–2023
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National Multiple Sclerosis Society (PI: Zamvil)Progressive MS Alliance, administered by National Multiple Sclerosis Society
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- Ravi Dandekar, MS,
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(1) University of California, San Francisco
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- Gregory F. Wu, MD, PhD,
1. Commercial - Genentech2. Commercial - Sangamo
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editorial board of N2 - no compensation.editorial board of Journal of Neuroimmunology - compensation
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Commercial - GenentechCommercial - Banner LifesciencesGovernment - Department of Justice
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Commercial - EMD Serono, Biogen
PI, NIH R01NS083678, R21NS121818
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PI, National Multiple Sclerosis Society
Progentec
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Government - Department of Justice
- Wesley Wu, PhD,
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- John E. Pak, PhD,
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- Stephen L. Hauser, MD,
Serves on scientific advisory board for (1) Accure, (2) Alector, and (3) Annexon; serves on Board of Directors for (4) Neurona.
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(1) Harrison's Principles of Internal Medicine,McGraw-Hill Education
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(1) NGM Bio, (2) Moderna
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(1) F. Hoffmann La Roche, (2) Novartis AG; travel reimbursement and writing support for anti-CD20 related meetings and presentations.
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(1) NIH, R35NS111644, PI
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(1) Valhalla Foundation
Stock options received for service on board of directors for (1) Neurona
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Stock options received for service on scientific advisory board for (1) Accure, (2) Alector, (3) Annexon
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- Wendell Lim, PhD,
allogene; scifi foods, Burroughs Wellcome Fund
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Cell, Editorial BoardScience, Board of Reviewing Editors
1. Synthetic cytokine circuits to promote infiltration and clearance of immune excluded solid tumors; 2. Synthetic immuno-suppressive cells and methods of use thereof; 3. Therapeutic immune cell circuits for treating Pancreatic Ductal Adenocarcionoma; 4. series of six stable human leukemia (K562) tumor cell lines that differ in amount of HER2-BFP; 5. Chimeric antigen receptors with novel synthetic co-stimulatory domains composed of combinations of linear motifs. 6. Binding triggered regulation of protein degradation; 7. Antigen Explorer: A database of antigen combinations for improving tumor recognition in cancer T cell therapies; 8. Hybrid SynNotch Chimeric Antigen Receptors; 9. USE OF BRAIN-SPECIFIC ANTIGENS TO HOME, BLOCK AND DELIVER THERAPEUTIC TREATMENTS TO THE BRAIN; 10. Engineered Cellular Adhesion Molecules and methods of use thereof; 11. Synthetic receptors and receptor circuits for dual-antigen AND-gate control over expression of a therapeutic payload by engineered cells. 12. Use of MOG for Priming a Treatment for Glioblastoma; 13. A set of tissue-specific receptors to enable a targeted delivery of encoded payloads or cellular responses (cell tissue “GPS” system); 14. Synthetic cytokine circuits to promote targeted local expansion and activation of therapeutic immune cells. 15. A dynamic, autoregulatory circuit to control cytotoxic activity of chimeric antigen receptor cells and improve persistence, efficacy and control; 16.An OFF-switch for regulating synNotch induced cell activity; 17.Methods for regulating the activity of BCL-2 family member proteins in engineered cells to control cell survival/population size; 18. SYSTEMS AND METHODS FOR TARGETING CANCER CELLS; 19. Therapeutic immune cell circuits for treating GBM cancers (focused on EGFRviii negative) by targeting combinatorial antigens; 20.Therapeutic immune cell circuits for treating cancers with antigen heterogeneity; 21. Therapeutic immune cell circuits for treating EGFRviii positive GBM cancers with antigen expression heterogeneity; 22. Antigen density sensors for engineered T cells and their application in cell-based immunotherapies; 23. DNA as a scaffold for efficient and versatile loading of proteins on biodegradable polymeric particles for therapeutic use; 24. Binding-induced proteolytic transcriptional switches engineered using the Von Willdebrand Factor A2 domain as a mechanically regulated proteolytic...; 25. Engineered receptors that associate with the TCR complex to redirect antigen-induced T-cell activation; 26. Engineered receptors and receptor combinations for use in recognition of intracellular antigens; 27. Tumor specific antigen combinations as targets for engineered therapeutic immune cells with multi-antigen detection systems; 28. Chimeric Notch Receptor Platform: modular, engineerable class of contact-dependent cellular receptors in which extracellular inputs can be used to...; 29. A RNA-TARGETED PLATFORM FOR GENETIC PROGRAMMING AND METHODS OF USING SUCH SYSTEM; 30. AN "ON" SWITCH DESIGN AS A PHARMACOLOGICAL METHOD TO CONTROL CHIMERIC ANTIGEN RECEPTOR ACTIVITY FOR CELL-BASED IMMUNOTHERAPIES ("ON-SWITCH CHIMERIC; 31. LIGHT REGULATED SYSTEM FOR THE SPATIOTEMPORAL CONTROL OF SIGNALLING PROTEINS AND THEIR ACTIVITIES; 32. METHOD TO ENGINEER MAPK SIGNALING RESPONSES USING SYNTHETIC SCAFFOLD INTERACTIONS; 33. ENGINEERING DESIGNER PROTEIN SWITCHES USING MODULAR DOMAIN RECOMBINATION
Cell Signaling, Garland press, 2014
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NSF, DBI-1548297, co-Inv., 10/2021 – 09/2026NIH/NINDS, R35 NS105068, Inv., 12/2017-11/2025NIH/NCI, R01 CA220257, PI, 09/2018 – 07/2023NIH/NCI, U54CA244438, PI, 09/2019-08/2024Human Frontiers Science Program, RGP0025, co-PI,12/2019-11/2022NIH/NCI, R01 CA249018, PI, 12/2020-11/2026NIH/NCI, R01 CA253017, MPI, 04/2021-03/2027NIH/NCI, U01 CA265697, MPI, 09/2021-08/2026NIH/NCI , U19 CA264338-01, Inv.09/2021-08/2026CIRM, TRAN1-12905, Inv., 01/2022 – 02/2024NIH/NIDDK, R01 DK130969, MPI, 02/2022-01/2026NIH/NIDDK, R01 DK132547-01,MPI, 04/2022-03/2026NIH/NCI, R01 CA258789, PI, 08/2022-07/2027
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allogene, scifi foods
28. Chimeric Notch Receptor Platform: modular, engineerable class of contact-dependent cellular receptors in which extracellular inputs can be used to...; 29. A RNA-TARGETED PLATFORM FOR GENETIC PROGRAMMING AND METHODS OF USING SUCH SYSTEM; 30. AN "ON" SWITCH DESIGN AS A PHARMACOLOGICAL METHOD TO CONTROL CHIMERIC ANTIGEN RECEPTOR ACTIVITY FOR CELL-BASED IMMUNOTHERAPIES ("ON-SWITCH CHIMERIC
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allogene, scifi foods
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- Michael R. Wilson, MD* and
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Speaking honoraria from Genentech, Takeda, WebMD and Novartis.
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1. Patent pending for Kelch-like protein 11 (KLHL11) IgG as a marker of neurological autoimmunity.2. Patent pending for method for high percentage recovery of rare cells.
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Roche/Genentech, Novartis
1. National Institute of Neurological Disorders and Stroke, K08 NS096117, PI, 2016-20212. National Institute of Allergy and Infectious Diseases, R01AI145437, PI, 2019-20243. National Institute of Neurological Disorders and Stroke, U01NS120836, Co-PI, 2021-20264. National Institute of Neurological Disorders and Stroke, R01NS125693, Co-PI, 2022-20265. National Institute of Allergy and Infectious Diseases, R01AI158861, Co-I, 2021-20266. National Institute of Mental Health, R01MH122471, Co-PI, 2020-20257. National Institute of Allergy and Infectious Diseases, U19AI077439, Co-I, 2021-20238. National Institute of Neurological Disorders and Stroke, R35NS111644, Co-I, 2019-2027
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1. Sandler Foundation2. William K. Bowes, Jr. Foundation3. Westridge Foundation4. UCSF Weill Institute for Neurosciences5. Marcus Foundation7. National Multiple Sclerosis Society
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1. VeriPhi Health, 20222. Delve Bio, 2022
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- Scott S. Zamvil, MD, PhD*
Dr. Zamvil has received honoraria for serving on Data Safety Monitoring Boards for MS trials conducted by Opexa, BioMS, Teva Pharmaceuticals, Inc. and Eli Lilly and Co. Foundation.
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(1) Biogen - Speaker honoraria and advisory board meetings(2) Teva - Speaker honoraria and advisory board meetings(3) Alexion - Speaker honoraria and advisory board meetings(4) Novartis - Speaker honoraria and advisory board meetings(5) Horizon - Speaker honoraria and advisory board meetings
(1) Neurology, Neuroimmunology and Neuroinflammation,Deputy Editor, 2014-present
"Aquaporin-4 peptides and methods for using same"(SF2010-074; USF-461PRV (pending). The applicationdescribes the discovery of aquaporin-4 T cell determinantsin neuromyelitis optica patients and the use forantigen-specific tolerance.
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SSZ has served as a consultant to Biogen Idec, Teva Neuroscience, EMD-Serono, Genzyme, Novartis, Genentech/Roche, Horizon and Alexion.
Advanced Health Media, 2009-presentBiogen, 2009-presentAlexion, 2019-presentViela Bio, 2020Horizon, 2021-present
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(1) Biogen - speaker and advisory board meetings(2) Teva - speaker and advisory board meetings(3) Genentech - advisory board meeting(4) Novartis - advisory board meetings(5) Genzyme - advisory board meetings(6) Alexion - advisory board meeting(7) Horizon - advisory board meetings
NIH RO1 AI131624-O1A1NIH R21 NS10815990-01
NMSS RG 1701-26628NMSS RG 1801-29861
Alexander M. and June L. Maisin Foundation, PI
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- From the Department of Neurology (S.G., S.A.S., C.S., R.D., S.L.H., M.R.W., S.S.Z.), Weill Institute for Neurosciences, University of California San Francisco, CA; Department of Cellular Molecular Pharmacology (M.S., J.D., W.L.), University of California San Francisco Cell Design Institute, CA; Veterans Affairs Health Care System (R.A.S.), Department of Pathology, Stanford University School of Medicine, CA; Departments of Neurology and Pathology and Immunology (G.F.W.), Washington University in St. Louis, MO; and Chan Zuckerberg Biohub (W.W., J.E.P.), San Francisco, CA.
- Correspondence
Dr. Zamvil zamvil{at}ucsf.neuroimmunol.org
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