Preclinical Research Sets the Stage for Potential of CAR-NK Cell Therapy in Hematologic Malignancies

However, researchers also noted that similar to chimeric antigen receptor (CAR) T-cell therapy, CAR-NK cell treatment comes with its own set of challenges.

As the scientific community continues to determine ways to improve the efficacy and safety of chimeric antigen receptor (CAR) T-cell therapy, some research has looked at the potential of engineering a different type of cell to try and fight cancer: natural killer (NK) cells. In a recent review, researchers looked at the available data on the treatment approach across hematologic malignancies.

In their review, the researchers explained NK cells are effector cells in the immune system and engineering them can improve their antitumor abilities. The treatment approach could address some of the obstacles brought by CAR T-cell therapy, including the need to generate autologous CAR-T cell production for each specific patient and its economic implications. This is because CAR-NK cells can be produced from allogeneic donors. CAR-NK cells also carry a lower risk of cytokine release syndrome—a well-documented adverse reaction of CAR T-cell therapy.

However, the researchers also noted that similar to CAR T-cell therapy, CAR-NK cell treatment comes with its own set of challenges.

“Extensive research over the last few decades has shown the safety and credibility of using NK cells to treat cancer. However, NK cell therapy is still vulnerable to immunosuppressive mechanisms,” they wrote. “To resolve immunosuppression, improve cancer cell targeting, and finally enhance the antitumor effects of NK cells in cancer immunotherapy, acceptable and effective gene manipulation systems are required.”

The researchers noted that advanced efforts are underway to address and mitigate these key challenges and that with these efforts—and the promising results seen in preclinical models— CAR-NK cell treatments are on track to have “a strong and important contribution in cancer therapy.”

Preclinical research includes exploration in both leukemias and lymphomas—a large group of malignancies that come with diverse outcomes and prognoses. Thus far, results show CAR-NK cell treatment can treat the diseases by targeting antigens such as CD19, CD20, CD7, and CD5.

Some research has also shown that CAR-NK92 cells can overcome B cell acute and chronic leukemia resistance to parental NK cells, while other in vitro research of NK-92 cells showed promise in chronic lymphocytic leukemia. In aggressive T cell leukemias, researchers have shown that delivering CD5- or CD3-targeting CARs into the NK-92 cell line can elicit cytotoxic activity against both primary T cell lymphoma cells and T cell leukemia cell lines.

CAR-NK cells may also help overcome challenges resulting from treatment of heterogenous acute myeloid leukemia (AML), according to the researchers, who explained that AML blasts contain ligands that can be recognized through the activation of receptors in NK cells.

Non-Hodgkin lymphoma, another heterogenous disease, has also been a focus of CAR-NK treatment. Although success is often found in treating mature B-NHL with CD20 targeted rituximab, some B cell cancers are resistant to the treatment. A group of researchers found that, in vitro, anti-CD20 CAR-NK cells were able to significantly improve response to CD20+ B-NHL cells, including those sensitive and resistant to rituximab.


Marofi F, Saleh MM, Rahman HS, et al. CAR-engineered NK cells; a promising therapeutic option for treatment of hematological malignancies. Stem Cell Res Ther. Published online July 2, 2021. doi:10.1186/s13287-021-02462-y