The Application of Nanobody in CAR-T Therapy

Area of Science:

• Immunology
• Biotechnology
• Oncology

Background:

• Chimeric antigen receptor (CAR) T-cell therapy is a potent immune cellular therapy targeting specific cancer antigens.
• CAR constructs typically include an antigen-binding domain, transmembrane domain, and cytoplasmic signaling domain.

Purpose of the Study:

• To evaluate the application and efficacy of nanobodies as antigen-binding domains in CAR-T cell therapy.
• To explore the potential of nanobody-based CAR-T cells for treating various cancers.

Main Methods:

• Nanobodies were utilized as the antigen-binding domain in CAR constructs.
• CAR constructs were transduced into Jurkat cells, natural killer (NK) cells, or primary T cells.
• In vitro and in vivo studies were conducted to assess anti-tumor effects.

Main Results:

• Nanobody-based CAR structures demonstrated efficacy against over ten tumor-specific targets.
• Transduced CAR-T and CAR-NK cells exhibited significant anti-tumor activity.
• Anti-BCMA CAR-T cells modulated by nanobodies showed clinical effects comparable to single-chain variable fragment (scFv)-modulated CAR-T cells.

Conclusions:

• Nanobodies are a feasible and effective alternative to scFvs for CAR-T cell therapy development.
• Nanobody-based CAR-T therapy has shown promise from preclinical research to clinical application.
• This approach holds significant potential for developing advanced CAR-T therapies for challenging oncological indications.