Our clinical trials with CABA-201 (investigational CD19-CAR T cell therapy) in lupus and myositis are now recruiting.

CABA® Platform

Engineered T cell therapy platform to treat autoimmune diseases

Engineered T Cell Therapies

Engineered T cell therapy takes advantage of the T cell’s natural cell-killing capabilities. Through insertion of a gene encoding a specific receptor, these T cells are “trained” to target and destroy disease-causing cells. In the current method, T cells are sourced from a patient, modified and infused back into the same patient to take effect.

Background on CD19-CAR T Cells

CAR (Chimeric Antigen Receptor) T cells are T cells that have been engineered with additional receptors to identify specific proteins, called antigens, present on the surface of other cells. CAR-enabled targeting is the basis of numerous oncology treatments in cancer, where CAR T cell therapy has shown remarkable clinical success.

Most CARs have a similar structure that includes an extracellular target binding domain derived from antibodies and an intracellular signaling domain derived from the natural T cell receptor complex. The extracellular domain is typically a single-chain variable fragment (scFv) that binds specifically to a target antigen on cancer cells, such as CD19. Since 2017, four CD19-specific CAR T cell products have achieved regulatory approval in B cell cancers, including in types of leukemia and lymphoma.

Over the past couple of years, academic groups have published findings demonstrating the potential of CD19-CAR T to transform the course of autoimmune disease. Emerging data in patients with systemic lupus erythematosus, myositis and systemic sclerosis suggests the potential of a one-time treatment with a 4-1BB-containing CD19-CAR T cell therapy, with a high degree of similarity to CABA-201, to achieve robust improvement in clinical disease activity within 3 months of treatment, with a favorable safety profile. Complete responses have been observed beyond 2 years with no relapses as of November 2023.

  1. Mueller F, et al. CD19-Targeted CAR-T Cells in Refractory Systemic Autoimmune Diseases: A Monocentric Experience from the First Fifteen Patients [ASH abstract].

One Mission. One Platform. Two Approaches.

We believe that our CABA® platform – encompassing Chimeric Antigen Receptor T cells for Autoimmunity (CARTA) and Cabaletta’s proprietary Chimeric AutoAntibody Receptor T (CAART) cells – has potential applicability across a broad range of autoimmune diseases, including common and severe indications such as systemic lupus erythematosus (SLE), myositis, systemic sclerosis and generalized myasthenia gravis.

Our lead CARTA candidate, CABA-201, is a fully human CD19-CAR T cell therapy. Through transient depletion of all B cells following a single infusion, CABA-201 may be able to reset the immune system, providing potentially meaningful clinical responses to patients off immunosuppressive therapies.

The CAART product candidates employ highly specific targeting domains – custom-made for each autoimmune disease – designed to permanently eliminate only the disease-causing B cells. These B cells make up only a small fraction of all B cells, and by sparing the normal B cells, the goal is to eradicate the cause of disease while leaving the humoral immune system intact.

The Manufacturing Process

Our cell manufacturing process is similar to the process employed for a currently marketed and FDA-approved CAR T cell therapy. The manufacturing process consists of multiple steps:

  1. Withdrawing white blood cells from each patient;
  2. Stimulating certain T cells from these white blood cells, causing them to become activated and to proliferate;
  3. Combining patient T cells with our lentiviral delivery vector through a process known as transduction;
  4. Enabling the transduced T cells to multiply to obtain the desired dose; and
  5. Infusing the modified T cells back into the patient’s body.

One CABA™ Platform, Two Strategies to Address Autoimmune Diseases

1Mackensen, Andreas, et al. "Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus." Nature Medicine (2022): 1-9.
2Müller, Fabian, et al. "CD19-targeted CAR T cells in refractory antisynthetase syndrome." The Lancet (2023).
3Nunez D, et al. Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy. Mol Ther Methods Clin Dev 2023;31:101104. doi: 10.1016/j.omtm.2023.08.023.

Potential Advantages of Engineered T Cell Therapy

Targeting Autoimmune Diseases

CARTA product candidates, such as CABA-201, are designed for autoimmune diseases where B cells contribute to the initiation and/or maintenance of disease. They have the potential to reset the immune system through transient depletion of all B cells, with repopulation of the healthy B cells.

For autoimmune diseases with a limited number of well-defined pathogenic autoantibodies, CAART cells may provide an elegant biologic solution to disease. They are designed to destroy only disease-causing B cells, the source of pathogenic autoantibodies, while leaving a patient’s healthy immune system intact.

As therapies made of living cells, the CARTA and CAART product candidates can increase in number in the body, thus potentially enabling complete elimination of target cells and unlocking the possibility for a one-time treatment. Through these complementary approaches within the CABA™ platform, we aim to develop therapies with the potential to induce complete and durable remission for a broad range of autoimmune diseases.

The CABA® Platform

Our team developed the Cabaletta Approach to B cell Ablation (CABA®) platform to pursue the highest priority targets where we believe there is a biologic opportunity for treatment of autoimmune disease with one of our two cell therapy approaches.

The CABA Platform

* Illustrative list of diseases where biologic opportunity for cure or treatment with CAART or CARTA approach may be possible.

1 Koneczny, Inga. "Update on IgG4-mediated autoimmune diseases: new insights and new family members." Autoimmunity Reviews (2020): 102646.
2 Huijbers, Maartje G., et al. "IgG4-mediated autoimmune diseases: a niche of antibody-mediated disorders." Annals of the New York Academy of Sciences 1413.1 (2018): 92.
3 Ludwig, Ralf J., et al. "Mechanisms of autoantibody-induced pathology." Frontiers in immunology 8 (2017): 603.
4 Suurmond, Jolien, and Betty Diamond. "Autoantibodies in systemic autoimmune diseases: specificity and pathogenicity." The Journal of clinical investigation 125.6 (2015): 2194-2202.
5 Xiao, Ze Xiu, Joseph S. Miller, and Song Guo Zheng. "An updated advance of autoantibodies in autoimmune diseases." Autoimmunity Reviews (2020): 102743.
6 Hampe, Christiane S. "B cells in autoimmune diseases." Scientifica 2012 (2012).

Posters & Publications

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