These CAR-based cell therapies can lead to dramatic clinical responses and represent a substantial step forward in the treatment of B-cell malignancies. However, they face significant challenges for wide-spread adoption, the foremost of which is the cost and complexity of manufacturing. Significant drivers of the cost and complexity are the means of cell engineering and the autologous nature of the treatment.
NK cells represent a promising avenue for cell therapy as they: i). rapidly kill tumors in an antigen-independent fashion; ii). represent an allogeneic source of cells for simplified manufacturing and treatment of patients with compromised immune systems; and iii). have established clinical safety and modest anti-tumor efficacy upon transfer of autologous or allogeneic cells.
NK cells have historically proven difficult to engineer. First generation NK-CAR engineering using viral transduction demonstrated the cytotoxicity of anti-CD19 CAR NK cells against B-cell malignancies, however it posed challenges for more sophisticated engineering, commercial manufacturing and ultimately sacrificed clinical translation.
Non-viral engineering of NK cells using MaxCyte’s enabling electroporation technology5 provides significant improvements in efficiency and viability as well as a clinically-feasible, FDA-approved avenue to overcome manufacturing challenges and advance the field of CAR cell therapy.