Bibliographic Details
| Title: |
Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells. |
| Authors: |
Oh, Sangwook, Mao, Xuming, Manfredo-Vieira, Silvio, Lee, Jinmin, Patel, Darshil, Choi, Eun Jung, Alvarado, Andrea, Cottman-Thomas, Ebony, Maseda, Damian, Tsao, Patricia Y., Ellebrecht, Christoph T., Khella, Sami L., Richman, David P., O'Connor, Kevin C., Herzberg, Uri, Binder, Gwendolyn K., Milone, Michael C., Basu, Samik, Payne, Aimee S. |
| Source: |
Nature Biotechnology; Sep2023, Vol. 41 Issue 9, p1229-1238, 10p |
| Abstract: |
Muscle-specific tyrosine kinase myasthenia gravis (MuSK MG) is an autoimmune disease that causes life-threatening muscle weakness due to anti-MuSK autoantibodies that disrupt neuromuscular junction signaling. To avoid chronic immunosuppression from current therapies, we engineered T cells to express a MuSK chimeric autoantibody receptor with CD137-CD3ΞΆ signaling domains (MuSK-CAART) for precision targeting of B cells expressing anti-MuSK autoantibodies. MuSK-CAART demonstrated similar efficacy as anti-CD19 chimeric antigen receptor T cells for depletion of anti-MuSK B cells and retained cytolytic activity in the presence of soluble anti-MuSK antibodies. In an experimental autoimmune MG mouse model, MuSK-CAART reduced anti-MuSK IgG without decreasing B cells or total IgG levels, reflecting MuSK-specific B cell depletion. Specific off-target interactions of MuSK-CAART were not identified in vivo, in primary human cell screens or by high-throughput human membrane proteome array. These data contributed to an investigational new drug application and phase 1 clinical study design for MuSK-CAART for the treatment of MuSK autoantibody-positive MG. A muscle autoimmune disease is treated in mice with CAAR T cells. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
