Unleashing Immune Cells on Autoimmune Disease

2025 AAAS Annual Meeting | February 15, 2025

Achieving an immune system reset: The next act in CAR T therapy

ACR Convergence 2024 | November 18, 2024

Safety and efficacy of CABA-201, a fully human, autologous 4-1BB anti-CD19 CAR T cell therapy in patients with immune-mediated necrotizing myopathy and systemic lupus erythematosus from the RESET-Myositis™ and RESET-SLE™ clinical trials

ACR Convergence 2024 | November 17, 2024

Correlative Studies of CABA-201, a Fully Human, Autologous 4-1BB Anti-CD19 CAR T Cell Therapy in Patients with Immune-Mediated Necrotizing Myopathy and Systemic Lupus Erythematosus from the RESET-Myositis™ and RESET-SLE™ Clinical Trials

ACR Convergence 2024 | November 16, 2024

Autologous CD19 CART manufacturing from whole blood collection for the treatment of autoimmune disease

ESGCT 2024 | October 24, 2024

Clinical and translational findings following MuSK-CAART infusion without preconditioning in patients with Myasthenia Gravis (MuSCAARTes™ trial)

ESGCT 2024 | October 24, 2024

Correlative findings following DSG3-CAART infusion with & without preconditioning in patients with Pemphigus Vulgaris (DesCAARTes™ trial)

ESGCT 2024 | October 22, 2024

Case study of CD19-directed chimeric antigen receptor T-cell therapy in a subject with immune-mediate necrotizing myopathy treated in the RESET-Myositis™ phase I/II trial

Molecular Therapy | September 7, 2024

Jenell Volkov, Daniel Nunez, Tahseen Mozaffar, Jason Stadanlick, Mallorie Werner, Zachary Vorndran, Alexandra Ellis, Jazmean Williams, Justin Cicarelli, Quynh Lam, Thomas Furmanak, Chris Schmitt, Fatemeh Hadi-Nezhad, Daniel Thompson, Claire Miller, Courtney Little, David Chang, Samik Basu

Under compassionate use, chimeric antigen receptor (CAR) T-cells have elicited durable remissions in patients with refractory idiopathic inflammatory myopathies (IIM)1. Here, we report on the safety, efficacy, and correlative data of the first subject with the immune-mediated necrotizing myopathy (IMNM) subtype of IIM who received a fully human, 4-1BBz anti-CD19-CAR T-cell therapy (CABA-201) in the RESET-Myositis™ phase I/II trial (NCT06154252). CABA-201 was well-tolerated following infusion. Notably, no evidence of cytokine release syndrome (CRS) or immune effector-cell associated neurotoxicity syndrome (ICANS) was observed. CK levels decreased, and muscular strength improved post-infusion. Peripheral B-cells were depleted rapidly following infusion, and the subject achieved peripheral B-cell aplasia by day 15 post-infusion. Peripheral B-cells returned at 2 months post-infusion and were almost entirely transitional. Autoantibodies to SRP-9, SRP-72, SRP-54, and Ro-52, decreased relative to baseline whereas antibodies associated with pathogens and vaccinations remained stable. The infusion product consisted of predominantly CD4+ effector memory T-cells & exhibited in vitro cytolytic activity. Post-infusion, CABA-201 expansion peaked at day 15 and was preceded by a serum IFN-γ peak on day 8 with peaks in serum IL-12p40 and IP-10 on day 15. These data detail the safety, efficacy, and pharmacodynamics of CABA-201 in the first IMNM subject.

Preclinical specificity and activity of a fully human 4-1BB expressing anti-CD19 CART therapy for treatment-resistant autoimmune disease

Molecular Therapy: Methods & Clinical Development | May 20, 2024

Binghao J. Peng, Andrea Alvarado, Hangameh Cassim, Soprina Guarneri, Steven Wong, Jonathan Willis, Julia SantaMaria, Ashley Martynchuk, Victoria Stratton, Darshil Patel, Chien-Chung Chen, Yan Li, Gwendolyn K. Binder, Rebecca Dryer-Minnerly, Jinmin Lee, Samik Basu

Over 4% of the global population is estimated to live with autoimmune disease, necessitating immunosuppressive treatment that is often chronic, not curative, and carries associated risks. B-cells have emerged as key players in disease pathogenesis, as evidenced by partial responsiveness to B-cell depletion by antibody-based therapies. However, these treatments often have transient effects due to incomplete depletion of tissue resident B-cells. Chimeric antigen receptor T (CART) cells targeting B-cells have demonstrated efficacy in refractory systemic lupus erythematosus. To this end, we developed an anti-CD19 CART product candidate, CABA-201, containing a clinically evaluated fully human CD19 binder (IC78) with a 4-1BB costimulatory domain and CD3 zeta stimulation domain for treatment refractory autoimmune disease. Here we demonstrate specific cytotoxic activity of CABA-201 against CD19+ Nalm6 cells with no off-target effects on primary human cells. Novel examination of CABA-201 generated from primary T-cells from multiple autoimmune disease patients displayed robust CAR surface expression and effective elimination of the intended target autologous CD19+ B-cells in vitro. Together, these findings support the tolerability and activity of CABA-201 for clinical development in patients with autoimmune disease.

Deep serological profiling of autoimmune patients treated with anti-CD19 4-1BBz CAR T-cells

ASGCT 2024 | May 9, 2024

Autologous CD19 CART manufacturing from whole blood collection for the treatment of autoimmune disease

ASGCT 2024 | May 9, 2024

Preclinical specificity and activity of CABA-201, a fully human 4-1BB containing CD19 CAR T therapy for treatment-resistant myositis

GCOM 2024 | March 15, 2024

Preclinical Specificity and Activity of CABA-201, a Fully Human 4-1BB Containing CD19 CAR T Therapy for Treatment-Resistant Autoimmune Disease

Tandem 2024 | February 22, 2024

Deep serological profiling of SLE patients treated with anti-CD19 4-1BBz CAR T-cells

ACR Convergence 2023 | November 13, 2023

Samik Basu, Daniel Nunez, Darshil Patel, Jenell Volkov, Zachary Vorndran, Steven Wong, Andreas Mackensen, Georg Schett.

Correlative findings following DSG3-CAART infusion with and without preconditioning in patients with Pemphigus Vulgaris (DesCAARTes™ study)

ESGCT | October 25, 2023

Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy

Molecular Therapy: Methods & Clinical Development | September 1, 2023

Daniel Nunez, Darshil Patel, Jenell Volkov, Steven Wong, Zachary Vorndran, Fabian Müller, Michael Aigner, Simön Volkl, Andreas Mackensen, Georg Schett, Samik Basu

Chimeric antigen receptor (CAR) T cells targeting CD19+ B-cells have demonstrated efficacy in refractory systemic lupus erythematous (SLE). Although initial clinical data suggest that anti-CD19 CAR T-cell therapy is well tolerated and highly effective, the immunologic consequences of CAR T-cell therapy in SLE patients remain unclear. We profiled serum in six refractory SLE patients prior to and three months following CAR T-cell infusion. Three months post T-cell infusion, the inflammatory cytokines IL-6 and TNFα decreased in patient sera. This was accompanied by elevations in serum IL-7 and BAFF. Furthermore, SLE-associated antibodies dropped profoundly in five of six patients. Lastly, consistent with other reports of CD19 CAR T therapy in B-cell malignancies, we were able to show marginal impact of anti-CD19 CART therapy on pre-existing humoral immune responses in SLE patients. Together, these results provide insights into the mechanisms of efficacy of anti-CD19 CAR T-cell therapy in SLE.

Preclinical specificity and activity of CABA-201, a fully human 4-1BB containing CD19 CAR T therapy for treatment-resistant autoimmune disease

ASGCT 2023 | May 19, 2023

Correlative findings following DSG3-CAART infusion with and without combination preconditioning therapy in patients with PV (DesCAARTes study)

ASGCT 2023 | May 18, 2023

CAR T Cell to Treat Autoimmunity

ASGCT 2023 | May 16, 2023

Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells

Nature Biotechnology | January 19, 2023

Muscle-specifc tyrosine kinase myasthenia gravis (MuSK MG) is an autoimmune disease that causes life-threatening muscle weakness due to anti-MuSK autoantibodies that disrupt neuromuscular junction signaling. To avoid chronic immunosuppression from current therapies, we engineered T cells to express a MuSK chimeric autoantibody receptor with CD137-CD3ζ signaling domains (MuSK-CAART) for precision targeting of B cells expressing anti-MuSK autoantibodies. MuSK-CAART demonstrated similar efcacy as anti-CD19 chimeric antigen receptor T cells for depletion of anti-MuSK B cells and retained cytolytic activity in the presence of soluble anti-MuSK antibodies. In an experimental autoimmune MG mouse model, MuSK-CAART reduced anti-MuSK IgG without decreasing B cells or total IgG levels, refecting MuSK-specifc B cell depletion. Specifc of-target interactions of MuSK-CAART were not identifed in vivo, in primary human cell screens or by high-throughput human membrane proteome array.These data contributed to an investigational new drug application and phase 1 clinical study design for MuSK-CAART for the treatment of MuSK autoantibody-positive MG.

Characterization of DSG3-CAART cells prior to & following adoptive transfer in mPV

ESGCT Congress | October 13, 2022

A Phase 1 trial of DSG3-CAART cells in mucosal-dominant pemphigus vulgaris patients: preliminary data

EADV Congress | September 10, 2022

A Phase 1 trial of DSG3-CAART cells in mucosal-dominant pemphigus vulgaris patients: preliminary data

EADV Congress (Abstract Only) | August 29, 2022

A Phase 1 Trial Of DSG3-CAART Cells In mPV Patients: Early Cohort Clinical and Translational Data

SID 2022 | May 20, 2022

Characterization of DSG3-CAART Cells Prior To & Following Adoptive Transfer in mPV

ASGCT 2022 | May 17, 2022

A Phase 1 Trial of Targeted DSG3-CAART Cell Therapy in mPV Patients: Early Cohort Data

ASGCT 2022 | May 17, 2022

Chimeric autoantibody receptor (CAAR) T cells as a precision therapy for antigen-specific B cell depletion in PLA2R membranous nephropathy

ASN Kidney Week 2021 | November 5, 2021

Antigen-specific B-cell depletion for precision therapy of mucosal pemphigus vulgaris

The Journal of Clinical Investigation | August 20, 2020

Desmoglein 3 chimeric autoantibody receptor T cells (DSG3-CAART) expressing the pemphigus vulgaris (PV) autoantigen DSG3 fused to CD137-CD3ζ signaling domains, represent a precision cellular immunotherapy approach for antigen-specific B cell depletion. Here, we present definitive preclinical studies enabling a first-in-human trial of DSG3-CAART for mucosal PV. DSG3-CAART specifically lysed human anti-DSG3 B cells from PV patients and demonstrated activity consistent with a threshold dose in vivo, resulting in decreased target cell burden, decreased serum and tissue-bound autoantibodies, and increased DSG3-CAART engraftment.

MuSK chimeric autoantibody receptor (CAAR) T cells for antigen-specific cellular immunotherapy of myasthenia gravis

AAN 2020 Abstract 2769 | May 18, 2020

Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease

Science | July 8, 2016

Autoimmune diseases such as lupus and rheumatoid arthritis lack therapies that specifically target only the disease-causing cells. Inspired by the clinical success of using chimeric antigen receptor T cells to treat certain types of cancers, Ellebrecht et al. asked whether a similar approach might also work against antibody-driven autoimmune diseases.