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Updated: Jul 9, 2026
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Chimeric toxins inhibit growth of primary oral squamous cell carcinoma cells
Christopher Bachran1, Iring Heisler, Diana Bachran
1Zentralinstitut für Laboratoriumsmedizin und Pathobiochemie, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
Abstract:
Treatment of oral squamous cell carcinoma (OSCC) is currently based on surgery and radiotherapy. Prolongation of the survival time of patients with progressing tumors is infrequently achieved. To improve the therapeutic options, targeted therapies are a favorable alternative. Therefore, we analyzed the effect of a chimeric toxin (CT) named SE consisting of the epidermal growth factor and the plant protein toxin saporin from Saponaria officinalis. A second construct (SA2E) additionally contains a peptidic adapter designed to enhance efficacy of the CT in vivo and to reduce side effects. The IC(50) values for an OSCC cell line (BHY) were 0.27 nM and 0.73 nM for SE and SA2E, respectively, while fibroblasts remained unaffected. To investigate primary tumor cells, we developed a technique to analyze freshly prepared OSCC cells of 28 patients in a stem cell assay directly after surgery. Cells were treated for 1 h with the CTs, subsequently seeded into soft agar and colony growth determined after 1-2 weeks In spite of the short time of CT incubation, the amount of colonies was reduced to about 78% by 10 nM and to 69% by 100 nM of either toxin. A combined application of 10 nM SA2E with a saponin from Gypsophila paniculata reduced the amount of surviving cells to 68%. The results demonstrate the impact of the CTs on OSCC cells and depict that the stem cell assay is suitable to determine the potential of anti-tumor drugs before studies in vivo will be initiated.
Insights
Targeted chimeric toxins (CTs) show promise for oral squamous cell carcinoma (OSCC) treatment. These novel agents effectively reduced OSCC cell growth in a stem cell assay, suggesting potential for improved therapies.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Current oral squamous cell carcinoma (OSCC) treatments (surgery, radiotherapy) have limited efficacy for advanced tumors.
- Targeted therapies offer a promising alternative to improve patient survival rates.
- Chimeric toxins (CTs) combining growth factors with plant toxins are being explored for cancer treatment.
Purpose of the Study:
- To evaluate the efficacy of two novel chimeric toxins, SE and SA2E, against OSCC cells.
- To assess the potential of a stem cell assay for predicting anti-cancer drug efficacy in OSCC.
Main Methods:
- In vitro efficacy of SE and SA2E was determined using IC50 values on an OSCC cell line (BHY) and fibroblasts.
- A novel stem cell assay was developed to test freshly prepared primary OSCC cells from 28 patients.
- Cells were incubated with CTs and colony growth was measured after seeding into soft agar.
Main Results:
- SE and SA2E demonstrated potent cytotoxicity against OSCC cells (IC50 values in nM range) with minimal effect on fibroblasts.
- Short incubation with CTs significantly reduced colony formation in primary OSCC cells.
- Combined treatment with SA2E and a saponin further enhanced cell reduction.
Conclusions:
- Chimeric toxins SE and SA2E exhibit significant anti-tumor activity against OSCC cells.
- The developed stem cell assay is a valuable tool for pre-clinical evaluation of anti-cancer drugs for OSCC.
- These findings support the development of CTs as a targeted therapy for oral squamous cell carcinoma.
