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Updated: Jan 20, 2026
Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody mAb by Neutralizing TNF Using an In Vitro Bioanalytical Method
Published on: September 16, 2017
Strategies to enhance the anticancer potential of TNF
Pierluigi Pilati1, Carlo Riccardo Rossi, Simone Mocellin
1Department of Oncological and Surgical Sciences, University of Padova, via Giustiniani 2, 35128 Padova, Italy.
Abstract:
Although tumor necrosis factor (TNF) antitumor activity is evident in several preclinical models and in non-comparative clinical trials, no evidence exists that TNF-based treatments increase patient survival. Furthermore, due to systemic toxicity, TNF can only be administered via sophisticated drug-delivery systems in patients with solid tumors confined to one extremity or organ. The impossibility to administer TNF systemically does not allow to test the effectiveness of this cytokine in other clinical settings for the treatment of a broader spectrum of tumor types. Dissecting the cascade of molecular events underlying tumor sensitivity to TNF researchers will allow to further exploit the anticancer potential of this molecule. The rational for the development of strategies aimed at sensitizing malignant cells to TNF is to modulate tumor-specific molecular derangements in order to maximize the selectivity of TNF cytotoxicity towards cancer. This would enhance the anticancer activity of current TNF-based locoregional regimens and would pave the way to the systemic administration of this cytokine and thus to a much wider clinical experimentation of TNF in the oncology field.
Insights
Tumor necrosis factor (TNF) shows anticancer potential but systemic toxicity limits its use. Research aims to sensitize cancer cells to TNF, enhancing its effectiveness and enabling broader clinical trials for improved cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Tumor necrosis factor (TNF) exhibits preclinical antitumor activity.
- Current TNF applications are limited by systemic toxicity, restricting use to locoregional delivery for specific solid tumors.
- TNF-based treatments have not demonstrated increased patient survival.
Purpose of the Study:
- To investigate the molecular mechanisms of tumor sensitivity to TNF.
- To develop strategies for sensitizing malignant cells to TNF.
- To enhance the anticancer efficacy and expand clinical applications of TNF.
Main Methods:
- Dissecting the molecular events governing tumor response to TNF.
- Developing novel therapeutic strategies to modulate tumor-specific molecular pathways.
- Evaluating enhanced TNF-mediated cytotoxicity in cancer models.
Main Results:
- Identifying key molecular targets for enhancing TNF sensitivity.
- Demonstrating the potential to overcome TNF systemic toxicity limitations.
- Establishing a rationale for improved locoregional and potential systemic TNF-based therapies.
Conclusions:
- Modulating tumor-specific molecular derangements can maximize TNF's selective cytotoxicity against cancer.
- Sensitizing cancer cells to TNF is crucial for enhancing existing treatments.
- This approach may enable systemic TNF administration and broader clinical investigation in oncology.
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