# Manufacturing RNA-based CAR T cells to combat autoantibody-associated autoimmune disorders (AAAD)

> **NIH NIH R44** · CARTESIAN THERAPEUTICS, INC. · 2024 · $1,496,118

## Abstract

Autoantibody-associated autoimmune diseases (AAADs) are disorders in which dysfunctional plasma cells
(PCs) secrete autoantibodies that attack healthy tissue. Many AAADs attack the nervous system, such as
myasthenia gravis (MG), neuromyelitis optica, chronic inflammatory demyelinating polyneuropathy, Lambert-
Eaton syndrome, and necrotizing autoimmune myopathy. This R44 (Clinical Trial Not Allowed) will support
manufacturing of a new RNA-based cell therapy for neurological AAADs, and analysis of biomarkers from
patients who received the therapy. Chimeric antigen receptor T cell (CAR-T) therapy eliminates pathogenic
cells, such as PCs, by expressing engineered chimeric antigen receptors (CAR) in T cells isolated from a
patient; the T cells are then reinfused to kill the CAR’s target. All approved CAR T drugs rely on gene transfer
by DNA, which permanently modifies the genome. This poses several problems. DNA-modified CAR-T cells
multiply exponentially because CAR DNA replicates; this can cause life-threatening inflammation called
cytokine release syndrome (CRS). These CAR-T cells also require pre-treatment chemotherapy to create a
niche for cell proliferation. DNA-modified CAR-T cells are expensive to make and use clinically, because
frequent adverse events require close patient monitoring. These hurdles have limited CAR-T therapy only to
advanced cancers. Cartesian Therapeutics has designed a new approach that replaces DNA with RNA to
achieve transient, tunable CAR expression (rCAR-T). Unlike DNA-modified CAR T cells, CAR-encoding RNA
cannot replicate and decays in predictable fashion. Thus, the patient’s exposure to rCAR-T cells is determined
by cell dose. This avoids CRS and eliminates lymphodepleting chemotherapy. These advances create a
versatile, clinically-validated means to treat neurological AAADs. We have developed an rCAR-T that targets
B cell maturation antigen (BCMA). This marker is expressed on PCs – cells that produce autoantibodies in
AAADs. This therapy – “Descartes-08” – transiently expresses anti-BCMA CAR to target BCMA+ PCs after
infusion. MG is an AAAD in which BCMA+ PCs secrete autoantibodies that attack the neuromuscular junction,
causing severe muscle weakness. In the first successful Phase 2a trial of a cell therapy to treat autoimmunity
(NCT04146051), Descartes-08 conferred potent, safe, and long-lasting improvement in MG patients for 12
months or more, even though treatment was only 6-weeks (Lancet Neurology 2023). These benefits were
achieved without the toxicity, inpatient stays, or lymphodepletion needed in DNA-based CAR-Ts. Here we
propose key steps to develop rCAR-T as a new cell therapy option to treat neurological AAADs. The aims
are i) manufacture Descartes-08 product lots to complete the Phase 2 MG clinical trial, ii) Identify clinical
correlates in patient samples from ongoing randomized placebo-controlled trial (RCT) and iii) manufacture
Descartes-08 lots for expanded access and basket trial patients with othe...

## Key facts

- **NIH application ID:** 10921955
- **Project number:** 1R44NS137943-01
- **Recipient organization:** CARTESIAN THERAPEUTICS, INC.
- **Principal Investigator:** Christopher M Jewell
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,496,118
- **Award type:** 1
- **Project period:** 2024-06-07 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10921955

## Citation

> US National Institutes of Health, RePORTER application 10921955, Manufacturing RNA-based CAR T cells to combat autoantibody-associated autoimmune disorders (AAAD) (1R44NS137943-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10921955. Licensed CC0.

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