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Updated: Jun 24, 2025

Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
C1s targeting antibodies inhibit the growth of cutaneous squamous carcinoma cells
Liisa Nissinen1, Pilvi Riihilä1, Kristina Viiklepp1
1Department of Dermatology and FICAN West Cancer Centre Research Laboratory, University of Turku and Turku University Hospital, Hämeentie 11 TE6, 20520, Turku, Finland.
Abstract:
Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer. The incidence of cSCC is increasing globally and the prognosis of metastatic disease is poor. Currently there are no specific targeted therapies for advanced or metastatic cSCC. We have previously shown abundant expression of the complement classical pathway C1 complex components, serine proteases C1r and C1s in tumor cells in invasive cSCCs in vivo, whereas the expression of C1r and C1s was lower in cSCCs in situ, actinic keratoses and in normal skin. We have also shown that knockdown of C1s expression results in decreased viability and growth of cSCC cells by promoting apoptosis both in culture and in vivo. Here, we have studied the effect of specific IgG2a mouse monoclonal antibodies TNT003 and TNT005 targeting human C1s in five primary non-metastatic and three metastatic cSCC cell lines that show intracellular expression of C1s and secretion of C1s into the cell culture media. Treatment of cSCC cells with TNT003 and TNT005 significantly inhibited their growth and viability and promoted apoptosis of cSCC cells. These data indicate that TNT003 and TNT005 inhibit cSCC cell growth in culture and warrant further investigation of C1s targeted inhibition in additional in vitro and in vivo models of cSCC.
Insights
New targeted therapies show promise for advanced cutaneous squamous cell carcinoma (cSCC). Mouse monoclonal antibodies targeting C1s (TNT003 and TNT005) inhibited cSCC cell growth and promoted apoptosis, indicating potential for treating this common metastatic skin cancer.
Area of Science:
- Oncology
- Immunology
- Dermatology
Background:
- Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer with increasing incidence and poor prognosis.
- Current treatments lack specific targeted therapies for advanced or metastatic cSCC.
- Previous research identified abundant C1s expression in invasive cSCC cells and demonstrated that C1s knockdown reduces cSCC cell viability and growth.
Purpose of the Study:
- To investigate the therapeutic potential of targeting C1s in cSCC.
- To evaluate the efficacy of specific mouse monoclonal antibodies (TNT003 and TNT005) against human C1s in cSCC cell lines.
Main Methods:
- Utilized five primary non-metastatic and three metastatic cSCC cell lines expressing intracellular and secreted C1s.
- Treated cSCC cell lines with IgG2a mouse monoclonal antibodies TNT003 and TNT005 targeting human C1s.
- Assessed the effects of antibody treatment on cell growth, viability, and apoptosis.
Main Results:
- Treatment with TNT003 and TNT005 significantly inhibited the growth and viability of cSCC cells.
- Antibody treatment promoted apoptosis in cSCC cells.
- These findings were observed in both non-metastatic and metastatic cSCC cell lines.
Conclusions:
- Specific C1s-targeted monoclonal antibodies (TNT003 and TNT005) demonstrate efficacy in inhibiting cSCC cell growth and inducing apoptosis in vitro.
- Targeting C1s represents a promising therapeutic strategy for advanced and metastatic cSCC.
- Further in vitro and in vivo studies are warranted to validate these findings for clinical application.
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