Autologous Natural Killer Cell Therapy Produces Positive Results in 3 Sarcoma Case Studies

Nadezhda Omelchenko, MD

Advanced or metastatic sarcomas remain very difficult cancers to manage, and as such there is a great need for new treatment options for patients with these cancer types. Results from 3 case studies, presented at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16-20, in Los Angeles, California, indicate that natural killer (NK) cell therapy, used in combination with immune checkpoint inhibitors, may be a promising new treatment modality.

In an interview with CGTLive™, first author Nadezhda Omelchenko, MD, a research associate at Cancer Center of Southern California in Santa Monica, spoke about the rationale behind the study. The study utilized SNK01, a nongenetically-modified autologous NK cell therapy that is enhanced for cytotoxicity and able to be manufactured from material derived from patients who have been previously treated with chemotherapy. Omelchenko additionally went over the key results from each of the 3 patients, who had different forms of chemotherapy-resistant soft tissue sarcoma. The cases were unique in terms of dosing and other factors, but some positive results were observed in each.

CGTLive: Can you discuss the rationale behind this research?

Nadezhda Omelchenko, MD: The rationale of the study was to use people’s own innate immune system in a manner of anticancer activity. In this case, NK cells were used as the essential innate immune system cells. They were first taken from the peripheral blood, then enhanced and amplified in the laboratory ex vivo, and then administered back to the patients in an increased therapeutic dose. We used it in combination with immune checkpoint inhibitors, which not only inhibit immunosuppressive activity of T-cells, but also uncloak in the tumor microenvironment, which allows it to evade the immune system. It is believed the combination of these 2 immunotherapy drugs could lead to better and more effective increased activity in a person's own innate immune system, which has a crucial role in anticancer activity.

What were the key findings from this research presented at the conference?

As you can see in the poster (#1136), there are 3 excellent responses to the combination of the NK cell-based therapy with the immune checkpoint therapy. Right now, the clinical trial is [still] in progress, but the best responses to the trial are shown.

In the first case, the patient has desmoplastic round cell sarcoma and received 20 cycles of SNK01 as a monotherapy, which allowed him to achieve around 50% tumor size reduction. This was followed by debulking surgery, abdominal radiation, and chemotherapy. Then the patient received an additional 27 cycles of SNK01 in combination with immune checkpoint inhibitors, which the FDA advised. Right now, according to the patient’s recent scans, there is no evidence of disease.

The second case is a patient who had radiation-induced chondrosarcoma who was on a combination of SNK01 and immune checkpoint inhibitors for 18 cycles. This patient achieved about a 40% reduction in tumor size by only 4 months of treatment. Unfortunately, the patient died of sepsis after debulking surgery.

A third case reported is of a patient who has undifferentiated spindle cell sarcoma. The patient achieved stable disease, which means control of the tumor size. Right now, the patient has received 41 cycles of the combination of SNK01 and immune checkpoint inhibitors.

All 3 of these excellent cases showed the results of the trial are very promising and [indicate] even patients who already have advanced metastatic sarcoma could be treated effectively...

Transcript edited for clarity.

REFERENCE
1. Omelchenko N, Chawla N, Chua-Alcala V, et al. SNK-01 autologous enhanced natural killer cells and an immune checkpoint inhibitor control tumor growth in rare chemotherapy-resistant advanced soft tissue sarcomas. Presented at: American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting. May 16-20, 2023; Los Angeles, CA. Abstract #1136.