IPSIndian Journal of Pharmacology
Home  IPS  Feedback Subscribe Top cited articles Login 
Users Online : 8307 
Small font sizeDefault font sizeIncrease font size
Navigate Here
Resource Links
 »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
 »  Article in PDF (491 KB)
 »  Citation Manager
 »  Access Statistics
 »  Reader Comments
 »  Email Alert *
 »  Add to My List *
* Registration required (free)

In This Article
 »  Abstract
 » Introduction
 »  History of Devel...
 » Tnferade Biology
 » Mode of Action
 » Pharmacokinetics
 » Toxicity Profile
 » Clinical Trials
 » Future Prospects
 » Conclusions
 »  References
 »  Article Tables

 Article Access Statistics
    PDF Downloaded210    
    Comments [Add]    
    Cited by others 7    

Recommend this journal


 Table of Contents    
Year : 2015  |  Volume : 47  |  Issue : 5  |  Page : 479-483

TNFerade, an innovative cancer immunotherapeutic

Department of Microbiology, Mahatma Gandhi Medical College and Research Institute, Puducherry, India

Date of Submission24-Jan-2015
Date of Decision02-Jun-2015
Date of Acceptance16-Aug-2015
Date of Web Publication15-Sep-2015

Correspondence Address:
Dr. Arunava Kali
Department of Microbiology, Mahatma Gandhi Medical College and Research Institute, Puducherry
Login to access the Email id

Source of Support: Nil., Conflict of Interest: There are no conflicts of interest.

DOI: 10.4103/0253-7613.165190

Rights and Permissions

 » Abstract 

Tumor necrosis factor-α (TNF-α) is a chemokine with effective tumoricidal properties. However, severe systemic toxicity limits its use of as anticancer agent. TNFerade is a novel replication deficient adenovector based gene therapy, which enables the radiation inducible translation of human TNF-α gene specifically in cancer cells. When injected intratumorally, it has least systemic distribution. Consequently, it lacks TNF-α related systemic toxicity. Evidence suggests that it has superior tumoricidal activity and tolerability with minimum adverse effects. It has demonstrated its beneficial role in the treatment of a variety of cancers in terms of improving the disease free and overall survival, delaying tumor progression, and inducing tumor regression when used with concurrent radiotherapy or chemotherapy.

Keywords: Cancer immunotherapy, gene therapy, TNFerade, tumor necrosis factor-α

How to cite this article:
Kali A. TNFerade, an innovative cancer immunotherapeutic. Indian J Pharmacol 2015;47:479-83

How to cite this URL:
Kali A. TNFerade, an innovative cancer immunotherapeutic. Indian J Pharmacol [serial online] 2015 [cited 2023 Sep 25];47:479-83. Available from: https://www.ijp-online.com/text.asp?2015/47/5/479/165190

 » Introduction Top

Despite advances in diagnostic and treatment modalities, cancer has emerged as one of the leading cause mortality worldwide. As per current statistics, it accounts for 14.1 million new cases and 8.2 million deaths/year globally.[1] Approximately 32.6 million people in various countries are living with cancer.[1] This high mortality can be attributed to the various limitations in cancer treatment. Owing to uncontrolled multiplication, tissue invasion and hematogenous spread of cancer cells early containment and surgical resection is challenging.[2] Moreover, micrometastasis to distant areas of the body often occurs much before the first presentation of cancer.[3] Malignancies involving an inaccessible site, vital organs or in an advanced stage are less amenable to surgical removal en masse and their management largely depend on nonsurgical approaches such as chemotherapy and radiotherapy.[4],[5] Till date, no single chemotherapeutic agent has shown an optimum curative response without major adverse effects. Cancer relapse and recurrence frequently occur even with the multidrug combination. Poor bioavailability at the site of cancer, lack of specific action on tumor cells along with low therapeutic indices are the major limitations of cancer chemotherapy.[5] On the other hand, radiotherapy can be delivered locally directed at the cancer site. However, it is merely suppressive rather than curative.[5],[6] Radiotherapy is less likely to kill all cancer cells. It only controls the tumor progression temporarily. Furthermore, a subpopulation of cancer cells may develop radioresistance making it ineffective.[6] Consequently, there is a need for developing new strategies to treat cancers effectively. TNFerade is a novel genetic medicine which combined the anticancer actions of tumor necrosis factor-α (TNF-α) and concurrent radiotherapy. In this review, the biological, pharmacological, and clinical aspects of TNFerade as an anticancer drug and its future prospects are discussed.

 » History of Development Top

Adenovector have been used widely in gene therapy to deliver specific genes to target cells. It has success rate exceedingly higher than that of liposomes and other vectors.[7] The development of radiation responsive promoter-regulated recombinant protein expression system at the University of Chicago paved the path for TNF-α based cancer gene therapy.[8] TNFerade was developed by GenVec, Inc. in collaboration with Varian Medical Systems.[8],[9] GenVec's proprietary replication deficient adenovector was used to transfer human TNF-α gene with its promoter. It received Food and Drug Administration (FDA) approval for its phase I clinical trials in December 2000.

 » Tnferade Biology Top

TNFerade is a novel immunotherapeutic agent which delivers human TNF-α gene to cancer cells using replication-deficient adenoviral vector.[4] TNF-α is a potent proinflammatory cytokine produced by macrophages, lymphocytes, and fibroblasts in response to the infection and inflammation.[10] TNF-α suppression has been studied as an approach to develop anti-inflammatory agents.[11],[12] On the other hand, since it can induce apoptosis leading to tumor necrosis and regression, it has been considered as a candidate for cancer immunotherapy.[13] However, TNF-α, when administered systemically can cause severe adverse effects that are capillary leakage, disseminated coagulopathy, acidosis, and shock.[8],[14] The GenVec's proprietary adenovector of TNFerade is made replication deficient by deletion of E1 and E4 genes. Deletion of E4 gene also ensures no inhibition of host protein synthesis by this vector. Furthermore, E3 gene is nonessential for viral growthin vitro and it is removed in an attempt to accommodate 3 kb gene of TNF-α.[8] Following ligation of a radiation inducible promoter, early growth response (egr-1) gene to cDNA of TNF-α, it is cloned in E1, E3, E4 - deleted human adenovirus serotype 5 (Ad5). This is propagated in 293 ORF6 cells for optimum yield of TNFerade.

 » Mode of Action Top

TNFerade is administered as an intratumoral injection and used in conjunction with radiotherapy or chemotherapy for optimum tumoricidal effect.[15] The rationale behind this combination is the synergistic lethal action of TNF-α and radiotherapy/chemotherapy on cancer cells.[14] The egr-1 gene promoter has a key role in controlling the expression of TNF-α in response to radiation. It is proposed that radiation-induced reactive oxygen species (ROS) binds to CC (A + T rich) 6GG elements (known as CArG boxes) of the promoter and induce expression of TNF-α. ROS generated by chemotherapeutic agents like cisplatin also produce the same effect.[14] It is proposed that TNF-α radiosensitizes cancer cells and overcomes the limitations of radiotherapy, such as radioresistance and metastasis.[8] Chemotherapeutic agents such as cisplatin and fluorouracil were also found to have synergy with TNFerade when used concomitantly.[16],[17] Locally produced TNF-α damages tumor capillary endothelium, induces inflammatory cell infiltration in tumor interstitium and exerts a direct toxic effect on tumor cells.

 » Pharmacokinetics Top

TNFerade injected in locally binds with coxsackie/adenovirus receptor and are taken up by tumor cells where it causes radiation-induced translation of TNF-α.[8] Peak expression of TNF-α was detected 3 weeks after the transfection.[18] The TNF-α has minimum systemic distribution. In one study, TNF-α had the highest concentration in cancer site, while the blood level was minimum (15.6 pg/mL).[19] The lymphoreticular system has a critical role in the elimination of the adenovector. Inflammatory cells, especially phagocytes such as neutrophils and macrophages engulf and degrade adenovector.[8] Recruitment of these inflammatory cells is attributed to chemotactic cytokines. TNFerade itself accelerates its own metabolism. Interleukin-8 induced by the adenovector and TNF-α expressed by the tumor cells act as a chemoattractant for these phagocytes.[18] In addition, Ad5 being immunogenic mounts an immune response which also facilitates its metabolism.[7] Hence, this immune elimination is likely to be more prominent with faster kinetics on subsequent exposures.

 » Toxicity Profile Top

Evidence from animal studies and clinical trials suggests that TNFerade has a superior margin of safety with potent tumoricidal action.[8] TNFerade is devised for local action specifically at the cancer site. However, it was found to cause both systemic and local toxicity. Necrosis and ulceration at the injection site were frequently detected on the autopsy of tested animals.[19] Hematological alterations such as a decrease in red cells and hemoglobin, elevation of leucocyte and platelet counts have been noted even in the absence of concurrent radiation exposure.[19] Results from the animal model suggest, its toxicity is dose-dependent (i.e. higher toxicity with larger doses) and synergistic with radiation. TNFerade alone as well as with radiation was well tolerated over a dosage range of 4 × 109–4 × 1010 particle units (PU) in 20 nude mice with the intratumoral injection. In contrast, subcutaneous injection of TNFerade in BALB/c mice was associated with mortality (5%, 1 out of 20), especially when combined with radiotherapy (25%, 5 out of 20).[19] In another animal study, although the systemic injection of TNFerade caused death of one experimental animal, there were no physiological or anatomical abnormalities and the peak levels of TNF-α in blood following intravenous administration of 1 × 1011 PU TNFerade were 325 pg/mL and 260 pg/mL in BALB/c mice and nude mice, respectively.[8],[20]

Similar results were obtained in human patients enrolled in various clinical trials. Lower doses of TNFerade (4 × 109–4 × 1010 PU) was found to be associated with minimal blood levels of TNF-α (1–8 pg/mL) and least adverse effects.[21] Although, theoretically there is a risk of systemic toxicity and neighbouring tissue injury due to spill over of TNF-α in blood from the tumor, especially at high doses, no such events have been reported.[22] With few exceptions, serious or drug-limiting toxicities (DLT) and adverse drug interactions were not observed in most studies. Seiwert et al. reported thrombotic events as DLT at thedose of 3 (4 × 1011) PU.[23] In another study, cholangitis and pancreatitis were prominent at 1 × 1012 PU.[17] However, mild adverse effects such as fatigue, fever, chills, flu-like symptoms, nausea, vomiting, and pain at the injection site were common.[24]

 » Clinical Trials Top

Preclinical in vivo studies using animal models have demonstrated superior anticancer effects of TNFerade with minimum adverse outcomes. Various human cancerous cell lines (i.e. human esophageal adenocarcinoma, human laryngeal SQ-20B and human D54 malignant glioma) were commonly used as xenografts in nude mice which were subjected to intratumoral TNFerade injection in conjunction with radiotherapy.[8],[19] TNFerade was found to have selective action on tumor microvasculature resulting in a delay in tumor growth and tumor regression.[25] TNF-α also achieved a sustained level of the tumor without any spill over into plasma.

Clinical evidence of TNFerade therapy in cancer patients is available from 2001 onwards. Results of clinical trials which have evaluated various clinical parameters of TNFerade as an anticancer agent are listed in [Table 1]. The initial phase I trial data supports the use of the therapeutic combination of radiotherapy and chemotherapeutic agents with TNFerade, as these modalities had superior tumor control without any additional increase in toxicity. Chemotherapeutics such as cisplatin, 5-fluorouracil, hydroxyurea, gemcitabine, and capecitabine has been used successfully.[16],[23],[26],[27] TNFerade has been used over a dosage range of 4 × 107–1 × 1012 PU with 30–70 Gy concomitant radiation for wide variety of cancers namely cancers of pancreas, esophagus, rectum, breast, lung, skin, head-neck carcinoma, and soft tissue sarcoma.[16],[26],[28],[29],[30] Two studies reported that the tumor response to TNFerade was independent of histology.[20],[29] Although phase I clinical trials had improved overall and progression-free survival of cancer patients, in a phase III clinical trial for locally advanced pancreatic cancer standard of care plus TNFerade has failed to demonstrate a significant increase in patient survival in comparison to standard of care alone.[31] However, it was safe and had no serious toxicity.
Table 1: Clinical parameters of TNFerade therapy

Click here to view


In spite of promising results shown in earlier studies, GenVec discontinued phase III clinical trial of TNFerade trial in 2010. There are still many hurdles that have to be overcome before TNFerade gets FDA approval. While intratumoral injection of TNFerade is an easy and simple approach, it has its own inherent limitations. Owing to its nondiffusible nature, the effective tumoricidal effect of TNFerade is often restricted to a limited area near the needle track.[8] This is especially critical in case of large tumors. Although intratumoral injection is essential for its selective effect on cancer cells, this mode of administration precludes its systemic distribution. Hence, TNFerade is not suitable for control of metastasis and haematological cancers.[8] Furthermore, intratumoral TNFerade administration is challenging and often not feasible for cancers involving inaccessible sites. Although, there is no reported incidence, it may give rise to serious systemic toxicity in case of accidental spillage of from tumor into the blood. TNFerade requires radiotherapy for activation of its radiation-inducible promoter. However, synergistic toxicity has been noted with concomitant radiotherapy.[19] TNFerade also has adenovector related risks. Theoretically, there is a chance that the replication deficient adenovirus may mutate and becomes replication competent with pathogenic potential, leading to serious infection.[32] Furthermore, an immune response against adenovector may accelerate the metabolism of TNFerade on subsequent exposure. Hence, it may lack effective tumoricidal activity of repeated use.[7]

 » Future Prospects Top

Despite the limitations and the incongruous result of phase III trial in pancreatic cancer patients, TNFerade has significance as an anticancer agent because of its wide applications. The novel radiation-inducible promoter and adenovector technology synergistically combines the benefits of TNF-α immunotherapy and radiotherapy without the systemic toxicity. Furthermore, a variety of tumors in accessible sites can be effectively treated irrespective of histological types.[29] Intratumoral TNFerade injection precludes the need of isolated limb perfusion for the administration of chemotherapeutics in sarcoma and melanoma of extremities.[8] TNFerade administration to inaccessible tumors has been carried out using percutaneous, endoscopic, and endoscopic ultrasound (EUS) guided approaches with success.[4] These minimally invasive techniques obviate the difficulties of intratumoral administration of TNFerade in esophageal, gastric, rectal, bile duct, pancreatic, and lung cancers. EUS is especially important for pancreatic cancer. Preoperative TNFerade therapy does not interfere with tumor resection. On the contrary, it has been found to have a beneficial role as it results in tumor shrinkage.[16]

 » Conclusions Top

TNFerade associates the anticancer actions of TNF-α and concurrent radiotherapy and also permits the spatial and temporal control of TNF-α expression by selecting the appropriate timing and area for radiotherapy. The development of newer minimally invasive interventional drug delivery approaches has also extended its scope, especially in pancreato-biliary, gastrointestinal, and lung cancers. However, further studies are needed to determine its therapeutic potentials.

Financial Support and Sponsorship


Conflicts of Interest

There are no conflicts of interest.

 » References Top

GLOBOCAN 2012. Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. Lyon, France: International Agency for Research on Cancer; 2012. Available from: http://www.globocan.iarc.fr/Pages/fact_sheets_cancer.aspx. [Last accessed on 2015 Jan 20].  Back to cited text no. 1
Chang GJ. Challenge of primary tumor management in patients with stage IV colorectal cancer. J Clin Oncol 2012;30:3165-6.  Back to cited text no. 2
Iacovino JR. Breast cancer micrometastasis. J Insur Med 2014;44:72.  Back to cited text no. 3
Kim E, Telford JJ. Advances in endoscopic ultrasound, part 2: Therapy. Can J Gastroenterol 2009;23:691-8.  Back to cited text no. 4
Advantages and Disadvantages of Cancer Treatment; 2011. Available from: http://www.cancerlive.net/cancer-treatment/advantages-and-disadvantages- of-cancer-treatment/. [Last accessed on 2014 Oct 26].  Back to cited text no. 5
Merlano M, Mattiot VP. Future chemotherapy and radiotherapy options in head and neck cancer. Expert Rev Anticancer Ther 2006;6:395-403.  Back to cited text no. 6
Cavazzana-Calvo M, Thrasher A, Mavilio F. The future of gene therapy. Nature 2004;427:779-81.  Back to cited text no. 7
Kircheis R, Wagner E. Technology evaluation: TNFerade, GenVec. Curr Opin Mol Ther 2003;5:437-47.  Back to cited text no. 8
Varian and GenVec Reach Agreement to Jointly Develop New Therapy Products/Collaboration on Combining Radiotherapy with Novel Gene Constructs Aimed at Enhanced Therapy Techniques, New Products for Fighting Cancer. GenVec Inc Press Release; 1998. Available from: http://www.prnewswire.com/news-releases/varian-and-genvec-reach-agreement-to-jointly-develop -new-therapy-products-77337602.html. [Last accessed on 2015 Jan 20].  Back to cited text no. 9
Abbas AK, Lichtman AH. Basic Immunology: Functions and Disorders of the Immune System. Philadelphia, USA: Saunders/Elsevier; 2010.  Back to cited text no. 10
Oh YC, Jeong YH, Kim T, Cho WK, Ma JY. Anti-inflammatory effect of Artemisiae annuae herba in lipopolysaccharide-stimulated RAW 264.7 Cells. Pharmacogn Mag 2014;10 Suppl 3:S588-95.  Back to cited text no. 11
Kirana H, Jali MV, Srinivasan BP. The study of aqueous extract of Ficus religiosa Linn. on cytokine TNF-a in type 2 diabetic rats. Pharmacognosy Res 2011;3:30-4.  Back to cited text no. 12
Liu X, Zhang XF, Zheng ZW, Lu H, Wu X, Huang C, et al. The effect of chemotherapy combined with recombination mutant human tumor necrosis factor on advanced cancer. J Transl Med 2004;2:33.  Back to cited text no. 13
Kufe D, Weichselbaum R. Radiation therapy: Activation for gene transcription and the development of genetic radiotherapy-therapeutic strategies in oncology. Cancer Biol Ther 2003;2:326-9.  Back to cited text no. 14
Albelda SM, Sterman DH. TNFerade to the rescue? Guidelines for evaluating phase I cancer gene transfer trials. J Clin Oncol 2004;22:577-9.  Back to cited text no. 15
Chang KJ, Reid T, Senzer N, Swisher S, Pinto H, Hanna N, et al. Phase I evaluation of TNFerade biologic plus chemoradiotherapy before esophagectomy for locally advanced resectable esophageal cancer. Gastrointest Endosc 2012;75:1139-46.e2.  Back to cited text no. 16
Hecht JR, Farrell JJ, Senzer N, Nemunaitis J, Rosemurgy A, Chung T, et al. EUS or percutaneously guided intratumoral TNFerade biologic with 5-fluorouracil and radiotherapy for first-line treatment of locally advanced pancreatic cancer: A phase I/II study. Gastrointest Endosc 2012;75:332-8.  Back to cited text no. 17
Hallahan DE, Mauceri HJ, Seung LP, Dunphy EJ, Wayne JD, Hanna NN, et al. Spatial and temporal control of gene therapy using ionizing radiation. Nat Med 1995;1:786-91.  Back to cited text no. 18
Rasmussen H, Rasmussen C, Lempicki M, Durham R, Brough D, King CR, et al. TNFerade Biologic: Preclinical toxicology of a novel adenovector with a radiation-inducible promoter, carrying the human tumor necrosis factor alpha gene. Cancer Gene Ther 2002;9:951-7.  Back to cited text no. 19
Sharma A, Mani S, Hanna N, Guha C, Vikram B, Weichselbaum RR, et al. Clinical protocol. An open-label, phase I, dose-escalation study of tumor necrosis factor-alpha (TNFerade Biologic) gene transfer with radiation therapy for locally advanced, recurrent, or metastatic solid tumors. Hum Gene Ther 2001;12:1109-31.  Back to cited text no. 20
TNFerade Gene Therapy Causes Tumor Shrinkage at Lowest. Available from: http://www.prnewswire.com/news-releases/tnferade-gene-therapy-causes-tumor- shrinkage-at-lowest-doses-during-phase-i-clinical-trials-74090882.html. [Last accessed on 2015 Jan 20].  Back to cited text no. 21
TNFerade Gene Therapy Causes Tumor Shrinkage at Lowest Doses During Phase I Clinical Trials; 2001. Available from: http://www.prnewswire.com/news-releases/tnferade-gene-therapy-causes-tumor-shrinkage-at- lowest-doses-during-phase-i-clinical-trials-74090882.html. [Last accessed on 2015 Jan 20].  Back to cited text no. 22
Seiwert TY, Darga T, Haraf D, Blair EA, Stenson K, Cohen EE, et al. Aphase I dose escalation study of Ad GV.EGR.TNF.11D (TNFerade™ Biologic) with concurrent chemoradiotherapy in patients with recurrent head and neck cancer undergoing reirradiation. Ann Oncol 2013;24:769-76.  Back to cited text no. 23
Mundt AJ, Vijayakumar S, Nemunaitis J, Sandler A, Schwartz H, Hanna N, et al. APhase I trial of TNFerade biologic in patients with soft tissue sarcoma in the extremities. Clin Cancer Res 2004;10:5747-53.  Back to cited text no. 24
Gupta VK, Park JO, Jaskowiak NT, Mauceri HJ, Seetharam S, Weichselbaum RR, et al. Combined gene therapy and ionizing radiation is a novel approach to treat human esophageal adenocarcinoma. Ann Surg Oncol 2002;9:500-4.  Back to cited text no. 25
Citrin D, Camphausen K, Wood BJ, Quezado M, Denobile J, Pingpank JF, et al. Apilot feasibility study of TNFerade™ biologic with capecitabine and radiation therapy followed by surgical resection for the treatment of rectal cancer. Oncology 2010;79:382-8.  Back to cited text no. 26
Murugesan SR, King CR, Osborn R, Fairweather WR, O'Reilly EM, Thornton MO, et al. Combination of human tumor necrosis factor-alpha (hTNF-alpha) gene delivery with gemcitabine is effective in models of pancreatic cancer. Cancer Gene Ther 2009;16:841-7.  Back to cited text no. 27
Weichselbaum RR, Kufe D. Translation of the radio- and chemo-inducible TNFerade vector to the treatment of human cancers. Cancer Gene Ther 2009;16:609-19.  Back to cited text no. 28
McLoughlin JM, McCarty TM, Cunningham C, Clark V, Senzer N, Nemunaitis J, et al. TNFerade, an adenovector carrying the transgene for human tumor necrosis factor alpha, for patients with advanced solid tumors: Surgical experience and long-term follow-up. Ann Surg Oncol 2005;12:825-30.  Back to cited text no. 29
Senzer N, Mani S, Rosemurgy A, Nemunaitis J, Cunningham C, Guha C, et al. TNFerade biologic, an adenovector with a radiation-inducible promoter, carrying the human tumor necrosis factor alpha gene: A phase I study in patients with solid tumors. J Clin Oncol 2004;22:592-601.  Back to cited text no. 30
Herman JM, Wild AT, Wang H, Tran PT, Chang KJ, Taylor GE, et al. Randomized phase III multi-institutional study of TNFerade biologic with fluorouracil and radiotherapy for locally advanced pancreatic cancer: Final results. J Clin Oncol 2013;31:886-94.  Back to cited text no. 31
Douglas JT. Adenoviral vectors for gene therapy. Mol Biotechnol 2007;36:71-80.  Back to cited text no. 32


  [Table 1]

This article has been cited by
1 Role of Therapeutic Endoscopic Ultrasound in Management of Pancreatic Cancer: An Endoscopic Oncologist Perspective
Dushyant Singh Dahiya, Saurabh Chandan, Hassam Ali, Bhanu Siva Mohan Pinnam, Manesh Kumar Gangwani, Hashem Al Al Bunni, Andrew Canakis, Harishankar Gopakumar, Ishaan Vohra, Jay Bapaye, Mohammad Al-Haddad, Neil R. Sharma
Cancers. 2023; 15(12): 3235
[Pubmed] | [DOI]
2 Enhanced tumor inhibiting effect of 131I-BDI-1-based radioimmunotherapy and cytosine deaminase gene therapy modulated by a radio-sensitive promoter in nude mice bearing bladder cancer
Pan Hao, Chunli Zhang, Huan Ma, Rongfu Wang
Journal of Radiation Research. 2022;
[Pubmed] | [DOI]
3 Nucleic Acid-Based Approaches for Tumor Therapy
Simone Hager, Frederic Julien Fittler, Ernst Wagner, Matthias Bros
Cells. 2020; 9(9): 2061
[Pubmed] | [DOI]
4 Externally-Controlled Systems for Immunotherapy: From Bench to Bedside
María Tristán-Manzano, Pedro Justicia-Lirio, Noelia Maldonado-Pérez, Marina Cortijo-Gutiérrez, Karim Benabdellah, Francisco Martin
Frontiers in Immunology. 2020; 11
[Pubmed] | [DOI]
5 Modulating inflammation for cancer therapy
Birgit Ritter, Florian R. Greten
Journal of Experimental Medicine. 2019; 216(6): 1234
[Pubmed] | [DOI]
6 Targeting the death receptor signaling pathway as a potential therapeutic target in the treatment of colorectal cancer
Reyhaneh Moradi Marjaneh, Seyed Mahdi Hassanian, Niloofar Ghobadi, Gordon A. Ferns, Afshin Karimi, Mir Hadi Jazayeri, Mohammadreza Nasiri, Amir Avan, Majid Khazaei
Journal of Cellular Physiology. 2018; 233(10): 6538
[Pubmed] | [DOI]
7 The effects of tumor necrosis factor-a (TNF-a) rs1800629 and rs361525 polymorphisms on sepsis risk
Yixin Zhang, Xiaoteng Cui, Li Ning, Dianjun Wei
Oncotarget. 2017; 8(67): 111456
[Pubmed] | [DOI]


Print this article  Email this article


Site Map | Home | Contact Us | Feedback | Copyright and Disclaimer | Privacy Notice
Online since 20th July '04
Published by Wolters Kluwer - Medknow