NCT07144384

Intratumoral Injection of Standard Universal Donor Expanded Natural Killer Cells and TGF-beta Imprinted Natural Killer Cells for the Treatment of Skin Squamous Cell Carcinoma and Basal Cell Carcinoma

A Pilot Study Testing Intralesional Injection of Ex-Vivo Expanded Allogenic University Donor (UD) NK and TGFBi NK Cells in Patients With Cutaneous Keratinocyte Carcinomas

• Status: Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Kirsten Johnson · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This early phase I trial compares the safety, side effects and the biological or cellular activity of two types of universal donor (UD) natural killer (NK) cells (standard NK cells and transforming growth factor \[TGF\] beta imprinted \[TGF-beta-i\] NK cells), given directly into the tumor (intratumoral) in treating patients with skin (cutaneous) squamous cell carcinoma (SCC) or basal cell carcinoma (BCC). NK cells are a type of white blood cell that can recognize missing or incorrect proteins on tumor cells and then kill these tumor cells. It was recently discovered that infection with human cytomegalovirus (CMV), a common virus, leads to the development of a unique NK cell population. These "adaptive" NK cells have a more potent anti-tumor killing action. The TGF-beta-i NK cells used in this study are created using donors whose blood tests positive for CMV exposure. This may make them more effective at killing tumor cells. Giving UD TGF-beta-i NK cells may be safe, tolerable and/or more effective than standard UD expanded NK cells in treating patients with SCC or BCC.

Detailed description

PRIMARY OBJECTIVE: I. To determine the persistence of NK cell infiltration within biopsy-proven keratinocyte carcinomas following intra-tumoral injection of universal donor NK cells versus (vs) TGFbeta-resistant NK cells in a cohort of patients prior to their standard of care excision. SECONDARY OBJECTIVES: I. To assess the tolerability of NK cell cutaneous intra-tumoral injection measured by adverse events, described using Common Terminology for Cancer Related Adverse Events (CTCAE version \[v\] 5). II. To test the feasibility of a larger study using intra-tumorally injected NK cells. EXPLORATORY/CORRELATIVE OBJECTIVES: I. To assess clinical outcomes including size, area change, and visual appearance in clinical detection of keratinocyte carcinomas between injection and excision. II. To compare NK and other immune cell presence within the tumor/tumor microenvironment (TME) in cutaneous basal cell carcinomas (BCCs) vs squamous cell carcinomas (SCCs) injected with NK vs TGFbetai cells prior to excision. OUTLINE: Patients are randomized to 1 of 2 cohorts. COHORT I: Patients undergo standard of care (SOC) biopsy on day 0 and within 4 weeks (days 10-28) receive UD expanded NK cells intratumorally. Patients undergo SOC excision 4-8 weeks (days 28-56) after biopsy. COHORT II: Patients undergo SOC biopsy on day 0 and within 4 weeks (days 10-28) receive UD expanded TGF-beta-i NK cells intratumorally. Patients undergo SOC excision 4-8 weeks (days 28-56) after biopsy.

Conditions

• Skin Basal Cell Carcinoma
• Skin Nodular Basal Cell Carcinoma
• Skin Squamous Cell Carcinoma

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo SOC biopsy
BIOLOGICAL	Natural Killer Cell Therapy	Given UD expanded NK cells intratumorally
PROCEDURE	Surgical Procedure	Undergo SOC excision
BIOLOGICAL	Universal Donor Expanded TGF-beta-imprinted NK Cells	Given intratumorally

Timeline

• Start date: 2025-10-16
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2025-08-27
• Last updated: 2026-02-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study