Novel Combo With Engineered NK Cells in Early Trial for Breast Cancer

At the San Antonio Breast Cancer Symposium,Margaret Gatti-Mays, MD, MPH, of the Ohio State University in Columbus, discussed the ongoing phase Ib/II DiG NKs trial, which is assessing gemcitabine, transforming growth factor beta (TGF-β)-imprinted natural killer (NK) cells, with or without the GD2-binding antibody naxitamab (Danyelza) in metastatic GD2-expressing breast cancer.

In this exclusive MedPage Today video, she discusses what led to the trial, the technology involved, and what they hope to achieve.

Following is a transcript of her remarks:

The background behind the trial really goes back to some of the research I did when I was at the National Cancer Institute regarding transforming growth factor beta, or TGF-β. And so this is a pleiotropic cytokine that in late breast cancer can cause cancer to progress, whereas in early breast cancer actually can be tumor suppressive.

And so in metastatic breast cancers that secrete TGF-β, they tend to be very aggressive. It tends to lead to chemo resistance and immunotherapy resistance.

So in working with Dr. Dean Lee at Nationwide Children’s Hospital in Columbus, Ohio, he was able to create a TGF-β-resistant natural killer cell. And so through using the healthy cells of patients that do not have cancer, he was able to collect them through the blood, was able to then engineer them by expanding them through IL [interleukin]-21 and then exposing them to TGF-β. This created natural killer cells that then were resistant to TGF-β. And so that product is created at the cell therapy lab at Ohio State.

And so around the time that we started discussing the trial, we wanted to look for a companion or chemotherapy combination to use with the natural killer cells. Natural killer cells are often used with chemotherapy almost to augment the chemotherapy activity.

And so in this clinical trial, we are using gemcitabine to help with cytotoxic killing of the cancer cells. Gemcitabine also increases androgen presentation and has a lot of very positive immune effects that can augment natural killer cell cytotoxicity as well.

In addition to using gemcitabine and the natural killer cells that are TGF-β imprinted, we also are combining an anti-GD2 antibody called naxitamab that’s provided by Y-mAbs. Naxitamab, as I said, is an anti-GD2 antibody. It’s currently approved in pediatric neuroblastoma, but several solid tumors in addition to neuroblastoma also expressed GD2.

Breast cancers are estimated… approximately 60% of breast cancers in some studies expressed GD2. And so we’re hoping to use the combination of the gemcitabine first to try to kill the cancer cells using the naxitamab to help increase the antigen presentation and the targeting of the cancer cells. And then using the natural killer cells to really hopefully augment the cytotoxic killing of the other two agents.