Title:CAR-NK Cells for Cancer Therapy: Molecular Redesign of the Innate
Antineoplastic Response
Volume: 22
Issue: 4
Author(s): Oscar Cienfuegos-Jimenez, Eduardo Vazquez-Garza and Augusto Rojas-Martinez*
Affiliation:
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud. Monterrey CP 64710, Mexico
Keywords:
Chimeric antigen receptor, NK cells, adoptive cell transfer, immunotherapy, cancer, gene therapy, synthetic biology.
Abstract: The Chimeric Antigen Receptor (CAR) has arisen as a powerful synthetic biology-based
technology with demonstrated versatility for implementation in T and NK cells. Despite CAR T
cell successes in clinical trials, several challenges remain to be addressed regarding adverse events
and long-term efficacy. NK cells present an attractive alternative with intrinsic advantages over T
cells for treating solid and liquid tumors. Early preclinical and clinical trials suggest at least two
major advantages: improved safety and an off-the-shelf application in patients due to its HLA independence.
Due to the early stages of CAR NK translation to clinical trials, limited data is currently
available. By analyzing these results, it seems that CAR NK cells could offer a reduced probability
of Cytokine Release Syndrome (CRS) or Graft versus Host Disease (GvHD) in cancer patients, reducing
safety concerns. Furthermore, NK cell therapy approaches may be boosted by combining it
with immunological checkpoint inhibitors and by implementing genetic circuits to direct CAR-bearing
cell behavior. This review provides a description of the CAR technology for modifying NK
cells and the translation from preclinical studies to early clinical trials in this new field of immunotherapy.