A novel human tumor necrosis factor alfa mutein, F4614, inhibits in vitro and in vivo growth of murine and human hepatoma: Implication for immunotherapy of human hepatocellular carcinoma

  title={A novel human tumor necrosis factor alfa mutein, F4614, inhibits in vitro and in vivo growth of murine and human hepatoma: Implication for immunotherapy of human hepatocellular carcinoma},
  author={Yoshinari Atarashi and Satoshi Yasumura and Shuji Nambu and Yuko Yoshio and Jun Murakami and Toshio Takahara and Kiyohiro Higuchi and Akiharu Watanabe and Keizo Miyata and M. Kato},
Although treatment for hepatocellular carcinoma (HCC) has recently improved, most patients still relapse and die from this disease. The development of new therapeutic and preventive strategies for HCC is, therefore, required. A novel mutant protein (mutein) of human tumor necrosis factor alfa (TNF‐α mutein F4614,1SSSRGDSD··· 29V ··· 155L) was developed to decrease several adverse effects of TNF‐α. F4614 is known to lack hypotensive effects of human TNF‐α without losing its anti‐tumor effect in… Expand
Human tumor necrosis factor-alpha mutant RGD-V29 (F4614) shows potent antitumor activity and reduced toxicity against human tumor xenografted nude mice.
RGD-V29 appears to be a low-toxicity mutant of rhTNF that shows preferential activity towards tumors, and therefore merits further investigation in pre-clinical and clinical studies. Expand
Antigen-specific immunotherapy for human papillomavirus 16 E7-expressing tumors grown in the liver.
The data suggest that vac-Sig/E7/LAMP-1 is an effective vaccine for controlling E7-expressing tumors grown in the liver and the model suggests that antigen-specific immunotherapy may represent a powerful tool for treating liver tumors with characterized tumor-specific antigens. Expand
Evaluation of serum iron and ferritin in different treatment regimens for chronic hepatitis C virus
It can be concluded that serum ferritin increases in HCV patients treated with combined pegylated interferon--alfa (PEG-IFN)-ribavirin than the other treatment regimens. Expand
Identification of the heparin-binding domain of TNF-alpha and its use for efficient TNF-alpha purification by heparin-Sepharose affinity chromatography.
The N-terminus of the trimeric TNF-alpha molecule comprises two basic arginines within the short amino-acid sequence VRSSSR, which is here shown to be essential for binding of TNF-alpha toExpand
Depression, immunity, and survival in patients with hepatobiliary carcinoma.
PURPOSE The aims of the present study were to assess the prevalence of depressive symptoms at diagnosis, test the association between depressive symptoms and survival, and preliminarily test aExpand
Cancer-related symptom clusters, eosinophils, and survival in hepatobiliary cancer: an exploratory study.
Cancer-related symptoms, particularly pain and depression, were associated with increased percentages of eosinophils and survival and the presence of symptoms may reflect tumor cell death and be indicative of response to treatment, or other processes, in patients with HBC. Expand


Novel muteins of human tumor necrosis factor with potent antitumor activity and less lethal toxicity in mice
V29 showed potent anti‐tumor activity in 3 consecutive injection schedules despite the decreases in toxicity compared with rhTNF, suggesting that V29 merits further investigation in pre‐clinical and clinical trials. Expand
Recombinant human tumor necrosis factor-α: evidence of an indirect mode of antitumor activity
The results suggest that rTNF-α is a unique antitumor drug with potent necrotizing activity against solid tumors in mice, and that this activity may derive from indirect mechanisms related to the growth of tumors and not to the direct cytotoxicity of the drug. Expand
Recombinant human tumor necrosis factor--II. Antitumor effect on murine and human tumors transplanted in mice.
Recombinant human tumor necrosis factor (rHu-TNF) was found to exhibit potent antitumor activities not only against murine tumors but also against human tumors, i.e. HMV-2 melanoma, PC-10 lung carcinoma and GOTO neuroblastoma, heterotransplanted in nude mice. Expand
Novel Mutein of Tumor Necrosis Factor α (F4614) with Reduced Hypotensive Effect
Results indicated that F4614 has several advantages as a systemic therapeutic drug in the treatment of cancer, and evidence that the Arg → Val mutation at position 29 is largely responsible for the reduced hypotensive effect is presented. Expand
Recombinant human tumor necrosis factor‐α: Thrombus formation is a cause of anti‐tumor activity
The results suggest that rTNF‐α selectively stems the blood flow in newly formed microcapillaries in 7‐day‐old tumor tissue, eventually leading to autolysis of the tumor cells. Expand
Murine tumor cells transduced with the gene for tumor necrosis factor-alpha. Evidence for paracrine immune effects of tumor necrosis factor against tumors.
TNF-producing tumor cells could function in a paracrine fashion by inhibiting the growth of unmodified, parental tumor cells implanted at the same site and this process requires the existence of intact host immunity. Expand
Recombinant human tumor necrosis factor-alpha: effects on proliferation of normal and transformed cells in vitro.
The observations indicate that the effects of rTNF-alpha on cell growth are not limited to tumor cells, but rather that this protein may have a broad spectrum of activities in vivo. Expand
Overcoming the metastasis-enhancing potential of human tumor necrosis factor alpha by introducing the cell-adhesive Arg-Gly-Asp sequence.
  • K. Miyata, Y. Mitsuishi, +4 authors M. Kato
  • Biology, Medicine
  • Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research
  • 1995
A mutein, F4168, of human tumor necrosis factor alpha containing the cell-adhesive Arg-Gly-Asp (RGD) sequence near the N terminus was constructed, indicating that the adhesive nature of the RGD sequence is conferred upon hTNF-alpha. Expand
Antitumor activity of murine tumor necrosis factor (TNF) against transplanted murine tumors and heterotransplanted human tumors in nude mice
TNF from mice had an antitumor activity against not only murine tumors but also human tumors, and in addition to direct cytotoxicity against tumor cells, TNF induced a host‐mediated factor which contributed to the antitumors effects. Expand
Interferon-γ and Tumor Necrosis Factor-α Treatment of Ex Vivo Human Carcinoma Cells Potentiates Their Interaction with Allogeneic Lymphocytes
Although the cytokine-induced increase in MHC and ICAM-1 on the low-expressor tumors were probably important to the interaction with lymphocytes, it is likely that other properties were also induced that contributed to the phenomenon. Expand