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 immuno-oncology treatments across the biotechnology industry, 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. More recent CARs include additional costimulatory domains, such as 4-1BB (CD137), to increase the engineered cells’ cytokine production and self-replication for a more durable and potent clinical result.

Two CD19-specific CAR T cell products, Kymriah® and Yescarta®, achieved regulatory approval in 2017 for types of cancers, including acute lymphoblastic leukemia (ALL) and diffuse large B cell lymphoma (DLBCL).

In September 2022, an academic group published findings Nature Medicine that showed the potential of CD19-CAR T to transform the course of autoimmune disease. In five patients with severe systemic lupus erythematosus (SLE), one-time treatment with a 4-1BB-containing CD19-CAR T cell therapy induced clinical remission of all five patients within three months after treatment, with mild CRS in 3/5 patients and no neurotoxicity observed. Healthy B cells repopulated in all patients within 5 months of treatment, and responses remained durable off all SLE-associated medications with 5-17 months of follow-up.1 Similar results were observed in a case report of a patient with anti-synthetase syndrome, a subtype of myositis, as published The Lancet in February 20232. These findings demonstrate the potential for CD19-CAR T to “reset the immune system,” potentially eliminating the cause of autoimmune disease with restoration of the healthy immune system.

  1. Mackensen, Andreas, et al. "Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus." Nature Medicine (2022): 1-9.
  2. Müller, Fabian, et al. "CD19-targeted CAR T cells in refractory antisynthetase syndrome." The Lancet (2023).

® These names are the registered trademarks of Novartis and Gilead Sciences, respectively.

One Mission. One Platform. Two Approaches.

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 dozens of autoimmune diseases, including common and severe indications such as systemic lupus erythematosus (SLE), rheumatoid arthritis, myositis and systemic sclerosis.

Our lead CARTA candidate, CABA-201, is based on a clinically-evaluated fully human CD19 binder containing a 4-1BB co-stimulatory domain. Through potential transient depletion of all B cells following a single infusion, CABA-201 may be able to reset the immune system by eliminating disease-causing B cells and allowing repopulation by healthy B cells, providing potentially meaningful clinical responses to patients without long-term immunosuppression.

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 leave the humoral immune system intact while eradicating the cause of disease.

The Manufacturing Process

Our current manufacturing process involves the assembly of the lentiviral delivery vector used to transport the applicable CAR or CAAR gene into the T cells, and is an approach similar to that used 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).
3Ellebrecht, Christoph T., et al. "Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease." Science 353.6295 (2016): 179-184.

Potential Advantages of Engineered T Cell Therapy

Targeting Autoimmune Diseases

CARTA product candidates 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 that constitute the humoral immune system and prevent disease.

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 enabling complete elimination of target cells and unlocking the potential 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 dozens of applicable B cell-mediated autoimmune diseases.

The CABA™ Platform

Our team developed the Cabaletta Approach to B cell Ablation (CABA™) platform to identify autoimmune diseases and to pursue the highest priority targets for our technology.

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

Learn more about our scientific research through posters at leading conferences and publications in peer-reviewed journals.

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