Monitoring for Infection-Like AEs Is Essential for CIML NK in GI Cancers

Cytokine-induced memory-like (CIML) natural killer (NK) cell immunotherapy combined with interleukin-2 (IL-2) can be accompanied by infection-like adverse effects (AEs) in patients with kidney or urothelial cancer, according to Wenxin (Vincent) Xu, MD. In addition to these AEs, patients may experience lowered blood counts because of required lymphodepleting chemotherapy preceding investigative treatment.

In an interview with Oncology Nursing News at the 2025 Kidney Cancer Research Summit, Xu, a genitourinary oncologist at the Dana-Farber Cancer Institute in Boston and Chestnut Hill, Massachusetts, explained the toxicity profile of the investigative therapy as the principal investigator of a phase 0 pilot study investigating CIML NK immunotherapy in patients with renal cell carcinoma and urothelial carcinoma (NCT06318871).

The trial requires that patients receive apheresis to collect NK cells, followed by predetermined standard-of-care lymphodepleting chemotherapy, then CIML NK therapy.

While CIML NK immunotherapy causes infection-like AEs such as fever, increased heart rate, and lower blood pressure that are commonly associated with immunotherapies, the preceding lymphodepleting chemotherapy may itself cause infection along with the catalog of AEs typically associated with chemotherapy. Risk of infection is especially important to monitor when patients are undergoing this type of therapy due to the combination’s suppression of patients’ immune systems.

Transcript

The actual protocol for this trial is that patients first undergo apheresis for collection of their immune cells, then undergo chemotherapy to make room in the immune system, then receive the cells, followed by IL-2. Each of these steps can have side effects.

Specifically, immune cell collection is comparable to a large blood collection. Patients can have temporary decrease in their circulating cells, which usually only lasts a few hours to a couple of days. Patients can sometimes have tingling from the cell collection.

The lymphodepleting chemotherapy is intended to suppress the immune system and make room for cells, so patients will certainly have lower blood counts. Patients have regular chemotherapy side effects, including fatigue, nausea, irritation or bleeding of the bladder, and increased risk for infection. That’s really a major one, because we’re intentionally suppressing the immune system.

Because the natural killer cells are the patient’s own cells that have been treated with cytokines, the cells usually don’t result in a big allergic reaction. They really are your own cells. However, they can result in an infection-like syndrome, where your body thinks it’s fighting an infection and may have fever, fast heart rate, low blood pressure, almost like a regular infection. The IL-2 also stimulates your immune system and can potentially cause fever or hypoxia.

This transcript has been edited for clarity and conciseness.

Reference

Memory-like natural killer (NK) cell therapy in patients with renal cell carcinoma or urothelial carcinoma. ClinicalTrials.gov. March 19, 2024. Updated June 11, 2025. Accessed July 23, 2025. https://clinicaltrials.gov/study/NCT06318871?id=NCT06318871&rank=1#study-record-dates