Cancer immunotherapy using NK cells in combination with monoclonal antibody drugs (mAbs) is expected to enhance the therapeutic efficacy of NK cells through antibody-dependent cellular cytotoxicity , which is facilitated by the binding of the Fc region with Fcγ receptors.

As we have previously reported, culture-expanded NK cells in combination with mAbs have higher IFN-γ and TNF-α production and cytotoxic activity against antigen-positive cancer cell lines than fresh blood-derived NK cells.

In this report, we present cases in which cancers refractory to standard treatments were markedly improved by combining the culture-expanded NK cells with mAbs.

Case 1 is a patient with diffuse large B-cell lymphoma. She was 85 years old, ineligible for R-CHOP, and placed on observation. However, by combining rituximab with autologous cultured NK cells, the lesions shrank and her quality of life remains good 15 months after starting treatment.

Case 2 is a 56-year-old patient with follicular lymphoma, who did not respond to rituximab monotherapy. He therefore received radiotherapy for cerebellar metastasis, bilateral adrenal tumors, and multiple cervical lymph node metastases, followed by rituximab and two weeks of intensive administration of autologous cultured NK cells and dendritic cells. There has been no relapse for two years.

Case 3 is a 60-year-old patient with Her2-positive breast cancer who developed metastases in the lung, liver, adrenal gland, lymph nodes, and bone lesions after surgery. After 7 weeks of intensive treatment with trastuzumab, pertuzumab, NK cells, and dendritic cells, the multiple metastases disappeared almost completely.

These results suggest that the adoptive transfer of cultured NK cells in combination with mAbs may be a useful tool for cancer immunotherapy in real-world clinical settings.