BAFF CAR-T Cells for Lupus

Overseen By Matthew A Spear, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Luminary Therapeutics

Must be taking: Corticosteroids, Hydroxychloroquine

Must not be taking: High dose steroids

Disqualifiers: Neuropsychiatric lupus, Active infection, HIV, Genetic syndromes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 14

Duration: 14 days per dose level

18 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase 1 study seeks to examine the safety and recommended phase 2 dose (RP2D) of BAFF-ligand CAR-T cells (LMY-920) in adult patients with refractory systemic lupus erythematosus (SLE). It is hypothesized that BAFF CAR-T cells will be safe and will improve SLE disease activity scores.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does require that you stop T cell targeted therapy more than 3 weeks before starting and reduce prednisone to 10 mg/day or less. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment LMY-920 for lupus?

Research shows that CAR T cells targeting CD19+ B cells have been effective in treating lupus in mice and have shown promise in early human studies. These studies indicate that this approach can lead to sustained B cell depletion, reduced disease symptoms, and improved outcomes in lupus models. ^{1 2 3 4 5}

Is BAFF CAR-T cell therapy safe for humans?

The safety of BAFF CAR-T cell therapy in humans hasn't been directly studied yet, but similar CAR-T cell therapies targeting CD19 have been effective and safe in mouse models of lupus, showing potential for future human trials. ^{1 2 3 6 7}

How is the treatment LMY-920 unique for lupus?

The treatment LMY-920 uses BAFF CAR-T cells, which are engineered immune cells designed to specifically target and deplete B cells, potentially leading to disease remission in lupus. This approach is unique because it directly modifies the patient's immune cells to combat the disease, unlike traditional treatments that often involve general immune suppression. ^{1 6 7 8 9}

Research Team

Dean Lee, PhD

Principal Investigator

Nationwide Children

Eligibility Criteria

This trial is for adults aged 18-69 with active systemic lupus erythematosus (SLE) who haven't responded to standard treatments like corticosteroids and hydroxychloroquine, or other drugs such as methotrexate. Participants must have a creatinine clearance of at least 30 ml/min, stable heart function with an ejection fraction ≥40%, good lung function (pulse oximetry ≥92% on room air), and liver enzymes within acceptable limits.

Inclusion Criteria

My condition did not improve after standard and additional treatments.

I rely on steroids for my condition.

I am taking specific medications but my disease is still active because I can't tolerate standard treatments.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive autologous BAFF CAR-T cells with dose escalation to determine the maximum tolerated dose

14 days per dose level

Staggered enrollment with safety monitoring every 14 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• LMY-920

Trial Overview The study is testing the safety and optimal dose for phase 2 of LMY-920, which are CAR-T cells targeting BAFF-ligand in patients with refractory SLE. The goal is to see if these modified immune cells can safely improve disease activity scores in SLE patients.

Participant Groups

Group I: BAFF CAR T Experimental Treatment 1 Intervention

Autologous BAFF CAR T Therapy

Who Is Running the Clinical Trial?

Luminary Therapeutics

Lead Sponsor

Trials

3

Recruited

70+

Nationwide Children

Collaborator

Trials

2

Recruited

50+

Findings from Research

Using CAR T cells to continuously deplete B cells leads to remission of lupus symptoms in mice that are genetically predisposed to the disease, suggesting a potential therapeutic strategy for lupus.

This study highlights the effectiveness of targeted cell therapy in managing autoimmune diseases, demonstrating that manipulating the immune system can result in significant health improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Slamming the brakes on lupus with CAR T cells. Clark, RA.[2019]

Complete and sustained depletion of CD19+ B cells using CD19-targeted CAR T cells was shown to be a highly effective therapy in lupus models, significantly reversing disease symptoms and extending lifespan in mouse models of lupus.

This approach demonstrated long-lasting effects, with CAR T cells remaining active for up to one year, suggesting that sustained B cell depletion could be a promising strategy for treating lupus in humans, warranting further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained B cell depletion by CD19-targeted CAR T cells is a highly effective treatment for murine lupus. Kansal, R., Richardson, N., Neeli, I., et al.[2021]

Anti-CD19 CAR-T cell therapy demonstrated effective B-cell depletion in a mouse model of systemic lupus erythematosus (SLE), showing both preventive and therapeutic benefits against the disease.

CAR-T cells using the 4-1BB costimulatory motif were found to be more effective than those using the CD28 motif, suggesting a promising strategy for optimizing treatment in SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of anti-CD19 CAR-T cells in a mouse model of systemic lupus erythematosus. Jin, X., Xu, Q., Pu, C., et al.[2022]

In a study of six patients with refractory systemic lupus erythematosus (SLE), anti-CD19 CAR T cell therapy was found to be well tolerated and led to a significant reduction in inflammatory cytokines IL-6 and TNFα three months after treatment.

The therapy also resulted in a marked decrease in SLE-associated antibodies in five out of six patients, suggesting a potential mechanism for its efficacy in managing SLE symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy. Nunez, D., Patel, D., Volkov, J., et al.[2023]

In a small study of five treatment-resistant patients with systemic lupus erythematosus (SLE), CD19 CAR T cell therapy led to significant clinical improvements and remission in all participants after 3 months, demonstrating its potential efficacy.

The treatment was well tolerated, with only mild cytokine release syndrome reported, suggesting a favorable safety profile for this innovative therapy in seriously ill SLE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Journal Club: Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Refractory Systemic Lupus Erythematosus. Boulougoura, A., Gendelman, H., Surmachevska, N., et al.[2023]

In a study of 52 patients with systemic lupus erythematosus (SLE), researchers identified a significantly expanded population of PD-1hiCXCR5-CD4+ T peripheral helper (Tph) cells that are linked to B cell activation and disease activity.

The presence of Tph cells correlated with clinical disease severity and B cell numbers in the kidneys of SLE patients, indicating their potential as a target for therapies aimed at modulating harmful B cell responses in this autoimmune disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1hiCXCR5- T peripheral helper cells promote B cell responses in lupus via MAF and IL-21. Bocharnikov, AV., Keegan, J., Wacleche, VS., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Slamming the brakes on lupus with CAR T cells. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Sustained B cell depletion by CD19-targeted CAR T cells is a highly effective treatment for murine lupus. [2021]

3. China pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of anti-CD19 CAR-T cells in a mouse model of systemic lupus erythematosus. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Journal Club: Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Refractory Systemic Lupus Erythematosus. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

BAFF overexpression and accelerated glomerular disease in mice with an incomplete genetic predisposition to systemic lupus erythematosus. [2007]

7. England pubmed.ncbi.nlm.nih.gov

Abnormal expression of BAFF and its receptors in peripheral blood and skin lesions from systemic lupus erythematosus patients. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Constitutive overexpression of BAFF in autoimmune-resistant mice drives only some aspects of systemic lupus erythematosus-like autoimmunity. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

PD-1hiCXCR5- T peripheral helper cells promote B cell responses in lupus via MAF and IL-21. [2022]