Anti-MUC1 nanobody can redirect T-body cytotoxic effector function

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Chimeric antigen receptors (CARs) are crucial for adoptive cancer immunotherapy, particularly against cancers lacking MHC or co-stimulatory molecules.
• Clinical use of CARs is hindered by immunogenic reactions caused by xenogenic antibody origins.
• Nanobodies, small antibody fragments with high human homology and low immunogenicity, offer a potential solution.

Purpose of the Study:

• To develop and evaluate a novel chimeric receptor utilizing an anti-MUC1 nanobody as the antigen-binding domain.
• To assess the efficacy of this nanobody-based CAR in targeting MUC1-positive cancer cells.
• To investigate the potential of nanobody CARs for reduced immunogenicity in cancer immunotherapy.

Main Methods:

• Constructed a chimeric receptor with an anti-MUC1 nanobody, CD28 and CD3zeta signaling domains, and an IgG3 spacer.
• Transfected the construct into Jurkat cells.
• Co-cultured transfected Jurkat cells with MUC1-positive MCF7 cells and analyzed IL2 secretion, Jurkat proliferation, and MCF7 cell death.

Main Results:

• The nanobody chimeric receptor successfully targeted MUC1-positive cancer cells.
• Demonstrated specific and efficient function of the nanobody-based chimeric receptor.
• Observed Jurkat cell proliferation and MCF7 cell death upon co-culture, indicating CAR activity.

Conclusions:

• Nanobody-based chimeric receptors can effectively target tumor-associated antigens like MUC1.
• The non-immunogenic nature of nanobodies makes these receptors promising for clinical applications.
• This approach represents a significant advancement in developing safer and more effective CAR immunotherapies.