Breaking the barrier: Synergistic 2B4.4-1BB signaling potentiates HER2-CAR NK cells to penetrate and destroy ADCC-resistant tumors

Key Points

• The aim is to investigate how dual 2B4.4-1BB signaling enhances the effectiveness of HER2-CAR NK-92 cells against ADCC-resistant tumors.
• Reprogramming of HER2-CAR NK-92 cells through dual 2B4.4-1BB signaling.
• Evaluation of tumor infiltration capabilities in ADCC-resistant tumor spheroids.
• Assessment of tumor remission duration after therapy.
• Dual signaling led to significant tumor infiltration and superior antitumor activity.
• Achieved long-lasting tumor remission in treated tumor models.
• Next-generation CAR-NK design effectively overcame immune resistance.