Abstract Details

Title CAR-T cell-mediated B cell depletion in central nervous system autoimmunity

Topic Multiple Sclerosis

Presentation(s) P1 - Poster Session 1 (9:00 AM-5:00 PM)
S1 - Virtual Abstract Data Blitz Presentations (8:00 AM-5:00 PM)

Poster/Presentation
Number 068

Objective Evaluate chimeric antigen receptor (CAR)-T cell mediated B cell depletion in experimental autoimmune encephalomyelitis (EAE).

Background CAR-T cells are autologous T cells expressing a non-MHC target antigen specific receptor. We tested whether anti-CD19 CAR-T cells, which more thoroughly deplete human B cell populations than monoclonal antibodies (mAbs), recapitulated the beneficial effects of B cell depletion in EAE.

Design/Methods Anti-CD19 CAR-T cells or control T cells that overexpressed green fluorescent protein were transferred into female wild-type C57BL/6 mice that had been pretreated with cyclophosphamide. EAE was induced by immunization with either recombinant human (rh) myelin oligodendrocyte protein (MOG) (B cell-dependent) or MOG peptide (p) 35-55 (B cell-independent). Mice were evaluated daily for clinical signs of EAE and weekly for peripheral B and T cell counts. B cell levels, T cell immune modulation and histology were assessed at peak disease and at termination.

Results In rhMOG-induced EAE, clinical scores and histologic lymphocyte infiltration were reduced in mice treated with cyclophosphamide and either anti-CD19 CAR-T cells or control T cells. B cell depletion was observed in peripheral lymphoid tissue and in the central nervous system (CNS) of mice treated with anti-CD19 CAR T cells, similar to effects of anti-CD20 mAbs. There was no difference in T cell modulation including Th1 or Th17 populations, but there was a trend towards increase in Treg populations in the periphery and CNS in the anti-CD19 CAR-T cell and control T cell treated animals. Clinical scores and histology did not differ among treatment groups in p35-55-induced disease.

Conclusions Anti-CD19 CAR-T cells thoroughly deplete B cells peripherally and within the CNS. Treatment also results in less severe rhMOG-induced disease, but it was independent of B cell depletion. Our results are consistent with human data indicating that anti-CD19 CAR-T cells deplete B cells across compartments, suggesting that they may hold promise for progressive MS.

Authors/Disclosures
Sasha Gupta, MD (University of California, San Francisco) PRESENTER	Dr. Gupta has nothing to disclose.
	No disclosure on file
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Stephen L. Hauser, MD (UCSF Weill Institute for Neurosciences)	Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NGM Bio. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moderna. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BD. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pheno Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nurix Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gilead. Dr. Hauser has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Accure. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alector. Dr. Hauser has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Annexon. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hinge Therapeutics. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Neurona. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Roche that is relevant to AAN interests or activities. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Novartis that is relevant to AAN interests or activities.
	No disclosure on file
Michael R. Wilson, MD, FAAN (University of California San Francisco)	Dr. Wilson has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Delve Bio. Dr. Wilson has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Cambridge Medical Experts. Dr. Wilson has stock in Delve Bio. The institution of Dr. Wilson has received research support from Genentech / Roche. The institution of Dr. Wilson has received research support from NIH. The institution of Dr. Wilson has received research support from Novartis. The institution of Dr. Wilson has received research support from National Multiple Sclerosis Society. The institution of Dr. Wilson has received research support from Fanconi Anemia Research Foundation. The institution of Dr. Wilson has received research support from Department of Defense. The institution of Dr. Wilson has received research support from Chan Zuckerberg Initiative. Dr. Wilson has received intellectual property interests from a discovery or technology relating to health care. Dr. Wilson has received intellectual property interests from a discovery or technology relating to health care. Dr. Wilson has received personal compensation in the range of $10,000-$49,999 for serving as a Expert Witness with US Dept of Justice.
Scott S. Zamvil, MD, PhD, FAAN (University of CA, San Francisco)	Dr. Zamvil has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genzyme. Dr. Zamvil has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Horizon. The institution of Dr. Zamvil has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. The institution of Dr. Zamvil has received research support from Sumaira Foundation. Dr. Zamvil has received personal compensation in the range of $5,000-$9,999 for serving as a Advisory Board with Genzyme. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board with Genentech. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board with Alexion.

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