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Novel CS1 CAR-T Cells and Bispecific CS1-BCMA CAR-T Cells Effectively Target Multiple Myeloma.

Vita Golubovskaya1, Hua Zhou1, Feng Li1,2

  • 1Promab Biotechnologies, 2600 Hilltop Drive, Richmond, CA 94806, USA.

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|October 23, 2021
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Summary

Novel chimeric antigen receptor T-cell (CAR-T) therapies targeting CS1 and bispecific CS1-BCMA antigens show promise for treating multiple myeloma (MM). These engineered T-cells effectively eliminate cancer cells and inhibit tumor growth in vivo.

Keywords:
BCMACAR-T cellsCS1cell therapychimeric antigen receptorimmunotherapymultiple myelomatumor antigen

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Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • Multiple myeloma (MM) is a fatal hematological cancer requiring novel therapeutic strategies.
  • Current treatments for MM have limitations, necessitating the development of innovative approaches.

Purpose of the Study:

  • To develop and evaluate novel chimeric antigen receptor T-cell (CAR-T) therapies targeting CS1 and bispecific CS1-BCMA antigens for multiple myeloma.
  • To assess the efficacy of CS1-CAR-T cells and bispecific CS1-BCMA-CAR-T cells in targeting and eliminating multiple myeloma cells.

Main Methods:

  • Generation of a novel CS1-specific antibody (clone 7A8D5) for CS1-CAR-T cell development.
  • Construction and testing of CS1-CAR-T cells and bispecific CS1-BCMA-41BB-CD3 CAR-T cells.
  • In vitro assays to assess target cell killing and cytokine secretion (IFN-gamma).
  • In vivo studies using MM1S multiple myeloma tumor models to evaluate tumor growth inhibition.

Main Results:

  • CS1-CAR-T cells demonstrated specific killing of CS1-expressing target cells and multiple myeloma cells, with IFN-gamma secretion.
  • Bispecific CS1-BCMA-CAR-T cells effectively killed both CS1 and BCMA expressing target cells, including CS1/BCMA-positive multiple myeloma cells, and secreted IFN-gamma.
  • Both CS1-CAR-T cells and bispecific CS1-BCMA-CAR-T cells significantly inhibited MM1S multiple myeloma tumor growth in vivo.

Conclusions:

  • Novel CS1-CAR-T cells and bispecific CS1-BCMA-CAR-T cells are effective in targeting and eliminating multiple myeloma cells.
  • These CAR-T cell therapies demonstrate significant anti-tumor activity in preclinical models.
  • The findings provide a strong foundation for future clinical trials of these novel immunotherapies for multiple myeloma.