Table 2.

Examples of treatment strategies targeting TNF-α in cancer clinical trials

Strategies	Major results	Tumor types	References
Systemic recombinant TNF	Systemic single-agent recombinant TNF had low objective response rates	Advanced tumors	[46, 49]
TNF combined with IFNγ	Low objective response rate and significant toxicity	Multiple cancer types	[47]
Isolated limb infusion/perfusion	Objective response rates range between 49 to 90%. This approach is limited by the site of the tumor, the presence of metastases, local toxicity, and the need for specialized centers	Melanoma Sarcoma	[39, 40]
TNFerade	TNFerade is an adenovector-based gene therapy activated by radiation to induce translation of the human TNF-α gene specifically in cancer cells In a randomized phase III of locally advanced pancreatic cancer, TNFerade with the standard of care did not show a significant survival benefit compared to the standard of care alone	Advanced solid tumors Pancreatic cancer	[48]
Anti-TNF drugs	TICIMEL explored adding anti-TNF agents’ infliximab or certolizumab to nivolumab and ipilimumab in advanced melanoma. The ORR of the certolizumab and infliximab cohorts were 63% and 46%, respectively. Both combinations were safe with the certolizumab cohort having higher rates of adverse events compared to infliximab	Melanoma	[42, 43]

Abbreviations: IFN interferon, ORR objective response rate, TNF tumor necrosis factor