Multifunctional Natural Killer Cell Engagers Targeting NKp46 Trigger Protective Tumor Immunity

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Developing therapies to enhance anti-tumor immunity is crucial.
• Bispecific T-cell engagers face challenges like toxicity.
• Novel strategies are needed for effective cancer immunotherapy.

Purpose of the Study:

• To generate and evaluate trifunctional natural killer cell engagers (NKCEs).
• To assess the efficacy and safety of NKCEs in preclinical cancer models.

Main Methods:

• Generation of trifunctional NKCEs targeting NKp46, CD16, and tumor antigens.
• In vitro potency assays comparing NKCEs with existing antibodies.
• In vivo studies in mouse models to evaluate pharmacokinetics, off-target effects, and tumor control.

Main Results:

• Trifunctional NKCEs demonstrated superior in vitro potency compared to clinical antibodies.
• NKCEs exhibited favorable in vivo pharmacokinetics and no off-target effects.
• Efficient control of solid and invasive tumor growth was observed in mouse models.

Conclusions:

• Trifunctional NKCEs represent a novel class of molecules for cancer treatment.
• These engagers offer a promising approach to enhance anti-tumor immunity.
• NKCEs show potential for improved cancer immunotherapy with reduced toxicity.