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

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.

Eligibility

Inclusion Criteria:

* Ohio State University patients \> 18 years old
* Diagnosis of ≥ 1cm keratinocyte carcinoma, accessible by intra-tumoral injection
* Confirmation of cutaneous SCC (cSCC) (10 patients total) or BCC (10 patients total) via diagnostic biopsy

  * BCC: Nodular or aggressive subtype
  * SCC: Well-differentiated or aggressive subtype with T1 or T2 staging by American Joint Committee on Cancer (AJCC) criteria
* Patient meets criteria for standard of care surgical treatment with either wide local excision or Moh's surgery
* Presence of residual clinical cancer ≥ 1cm at the time of baseline
* Willingness to follow up for residual cancer extirpation between 2-8 weeks after the injection

Exclusion Criteria:

* Planned or concurrent radiation or systemic treatment for solid tumor or hematologic malignancy including chemotherapies or immunotherapies received within 6 weeks of trial enrollment. These include but are not limited to methotrexate, 5-fluorouracil, vismodegib, cepilimumab, pembrolizumab, nivolumab, ipilimumab for any skin malignancy
* \< 18 years old
* A negative deep and peripheral margin status from the diagnostic biopsy
* Diagnostic biopsy with the following histopathologic characteristics:

  * BCC: Superficial subtype
  * SCC: SCC in situ (SCCIS)/Bowen disease, basosquamous, keratoacanthoma (KA)-type SCC, or tumor with \> T2 staging by AJCC criteria
* Any skin disease or active infection in the same area that may confound assessments
* Inability to follow-up for definitive treatment (surgical excision)
* Any other comorbidity or complication that in the opinion of the investigator could make the patient unsafe to participate in the study, such as:

  * Active infection
  * Pregnant women, women who are likely to become pregnant or are breastfeeding
  * Patients who received any other investigational drugs within the 30 days prior to screening visit

Conditions4

Locations1 site

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