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Updated: Oct 2, 2026
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Interleukin 4 receptor-directed cytotoxin therapy for human head and neck squamous cell carcinoma in animal models
Scott E Strome1, Koji Kawakami, Danielle Alejandro
1Department of Otolaryngology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Abstract:
Receptors for interleukin 4 (IL-4R) are overexpressed on the surface of various human solid tumors including renal cell carcinoma, glioblastoma, Kaposi's sarcoma, and head and neck squamous cell carcinoma (SCCHN). On the basis of this preferential receptor overexpression, a novel IL-4R-targeted cytotoxin, IL-4 (38-37)-PE38KDEL, was developed in which circularly permuted IL-4 [IL-4 (38-37)] was fused to mutated form of Pseudomonas exotoxin (PE38KDEL). Despite the recognized expression of the IL-4R on SSCHN, the utility of a receptor-specific fusion protein for the treatment of this disease remains unknown. The purpose of this study was to establish the utility of IL-4 (38-37)-PE38KDEL for the treatment of established SSCHN in animal models of human disease. Expression of IL-4R in SCCHN was confirmed by immunohistochemistry with eight of eight tissue sections expressing IL-4R. Protein synthesis inhibition assays demonstrated growth inhibition of two cell lines in IL-4 (38-37)-PE38KDEL in a dose-dependent fashion. In two SCCHN s.c. xenografted nude mouse models, i.p. and intratumoral injection of IL-4 (38-37)-PE38KDEL mediated tumor regression with no visual toxicity observed in any of the animals. Subcultured tumor cells after intratumoral treatment with IL-4 toxin did not develop resistance to the drug. These data demonstrate that IL-4 (38-37)-PE38KDEL is effective in mediating significant antitumor effects in SCCHN and may represent an attractive therapeutic option for patients with advanced cancers of the upper aerodigestive tract.
Insights
Interleukin 4 receptor (IL-4R) targeted cytotoxin IL-4 (38-37)-PE38KDEL effectively treats head and neck squamous cell carcinoma (SCCHN) in preclinical models. This novel therapy demonstrated significant tumor regression with no observed toxicity, offering a promising treatment option.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Biology
Background:
- Interleukin 4 receptor (IL-4R) is overexpressed on various human solid tumors, including head and neck squamous cell carcinoma (SCCHN).
- A novel IL-4R-targeted cytotoxin, IL-4 (38-37)-PE38KDEL, was developed by fusing circularly permuted IL-4 to a mutated Pseudomonas exotoxin (PE38KDEL).
Purpose of the Study:
- To evaluate the therapeutic utility of IL-4 (38-37)-PE38KDEL for treating established SCCHN in preclinical animal models.
- To confirm IL-4R expression in SCCHN tissues and assess the drug's efficacy and toxicity.
Main Methods:
- Immunohistochemistry was used to confirm IL-4R expression in SCCHN tissue samples.
- In vitro protein synthesis inhibition assays were performed to assess growth inhibition.
- SCCHN xenograft models in nude mice were used to evaluate in vivo efficacy via intraperitoneal and intratumoral injections.
Main Results:
- IL-4R expression was confirmed in all tested SCCHN tissue sections.
- IL-4 (38-37)-PE38KDEL demonstrated dose-dependent inhibition of SCCHN cell lines.
- In vivo studies showed significant tumor regression in SCCHN xenografts with no observable toxicity. Tumor cells did not develop resistance post-treatment.
Conclusions:
- IL-4 (38-37)-PE38KDEL exhibits significant antitumor effects against SCCHN.
- This targeted cytotoxin represents a potential therapeutic strategy for advanced upper aerodigestive tract cancers.
