Potential treatment under development for patients with mucocutaneous pemphigus vulgaris (mcPV)

Image credit: D@nderm

Eliminating the Cells Responsible for Autoimmune Disease

DSG3/1-CAART is being developed to treat mucocutaneous pemphigus vulgaris (mcPV), a B cell-mediated autoimmune disease that causes blistering of the skin and mucous membranes. mcPV is caused by autoantibodies that attack the cell adhesion proteins DSG3 and DSG1.

DSG3/1-CAART is designed to selectively target and kill the B cells that express the pathogenic autoantibodies while preserving the healthy B cells critical to immune function. We anticipate that much of what we learn from our DSG3-CAART program, including clinical trial design in the DesCAARTesTM trial, will inform and potentially accelerate the development of DSG3/1-CAART.

DSG3/1-CAART pipeline

Treatment with a Precise Technique

Current treatments for mcPV call for corticosteroids and generalized immune suppression. This therapeutic approach can be temporarily effective but carries a substantial risk of disease recurrence, severe infection, and even death. We are currently developing a new candidate therapy that targets only pathogenic B cells and their autoantibodies, and may, with minimal side effects, achieve durable remission of this disease.

About Pemphigus Vulgaris (PV)

PV is a chronic, life-threatening autoimmune disease characterized by delamination, or separation of the layers of the skin and/or mucous membranes. Autoantibodies directed to DSG3 and/or DSG1, which are proteins expressed in desmosomes, the rivets between epithelial cells, are responsible for disease. When these desmosomes fail, erosions and blisters appear on the skin and mucosa, increasing the patient’s susceptibility to potentially fatal infections.

The pathogenic DSG3 and DSG1 autoantibodies are produced by a small number of aberrant B cells, which express the same DSG3 and DSG1 autoantibodies on their surface. These DSG-specific autoantibodies are widely considered both necessary and sufficient to cause PV.

PV has two major subtypes:

  • Mucosal PV (mPV)—Characterized by DSG3 autoantibodies, affecting primarily mucosal surfaces—accounts for approximately 25% of patients with PV.
  • Mucocutaneous PV (mcPV)—Characterized by DSG3 autoantibodies and DSG1 autoantibodies, affecting both mucosal and skin surfaces—accounts for approximately 75% of PV.

Symptoms of mcPV include blisters on the skin as well as the mucous membranes, including the mouth, nose, throat, and genitals, causing high levels of pain and impairing the patient’s ability to eat, drink, or function normally.

Preclinical Studies

In Vitro Studies

CAAR development for mcPV, based on the targeting of DSG3- and/or DSG1-specific B cells, has shown promising preclinical results. DSG1 CAAR T cells specifically killed DSG1-specific B cells in vitro. In addition, we observed that with a 1:1 mixture of DSG3 and DSG1 CAAR T cells had killing capabilities without synergistic or antagonistic effect.

In Vivo Studies

The activity and toxicity of DSG3 and DSG1-CAAR T cells were evaluated using human skin xenografts in comparison to CART19 cells, which are known from human clinical trials not to cause direct skin toxicity. A 1:1 mixture of DSG3 and DSG1 CAAR T cells did not show off-target toxicity toward human skin.

Posters & Publications

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

Examine Our Findings


Interested in the overview? These presentations hit the right notes.