A clinical study assessing the tolerability and biological effects of infliximab, a TNF-α inhibitor, in patients with advanced cancer

Brown, Ewan; Charles, Kellie A.; Hoare, Susan; Rye, Ron; Jodrell, Duncan I.; Aird, Rhona; Vora, Rashmi; Prabhakar, Uma; Nakada, Marian T.; Corringham, Robert; DeWitte, Mark; Sturgeon, C.; Propper, David; Balkwill, Frances R.; Smyth, John F.

doi:10.1093/annonc/mdn054

Cited by 157 publications

(87 citation statements)

References 28 publications

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“…In terms of cancer, phase I/II trials of antagonists of IL-6, the IL-6 receptor, CCL2, CCR4 and CXCR4 are underway for a range of epithelial and haematopoietic malignancies. The first (phase I/II) clinical trials of TNF-α antagonists in patients with advanced cancer have resulted in disease stabilization and some partial responses [93][94][95] , particularly for those with renal-cell carcinoma 95 . Also, a structural analogue of thalidomide, lenalidomide, that inhibits production of several inflammatory cytokines has been shown to be active against advanced myeloma when combined with dexamethasone 96 .…”

Section: The Big Questionsmentioning

confidence: 99%

Cancer-related inflammation

Mantovani

Allavena

Sica

et al. 2008

Nature

9,568

112

7,934

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Links between cancer and inflammation were first made in the nineteenth century, on the basis of observations that tumours often arose at sites of chronic inflammation and that inflammatory cells were present in biopsied samples from tumours 1 . The idea that these processes are connected was out of favour for more than a century, but there has been a recent resurgence in interest. Several lines of evidence 1-4 (Box 1) -based on a range of findings, from epidemiological studies of patients to molecular studies of genetically modified mice -have led to a general acceptance that inflammation and cancer are linked.Epidemiological studies have shown that chronic inflammation predisposes individuals to various types of cancer. It is estimated that underlying infections and inflammatory responses are linked to 15-20% of all deaths from cancer worldwide 1 . There are many triggers of chronic inflammation that increase the risk of developing cancer. Such triggers include microbial infections (for example, infection with Helicobacter pylori is associated with gastric cancer and gastric mucosal lymphoma), autoimmune diseases (for example, inflammatory bowel disease is associated with colon cancer) and inflammatory conditions of unknown origin (for example, prostatitis is associated with prostate cancer). Accordingly, treatment with non-steroidal anti-inflammatory agents decreases the incidence of, and the mortality that results from, several tumour types [5][6][7] .The hallmarks of cancer-related inflammation include the presence of inflammatory cells and inflammatory mediators (for example, chemokines, cytokines and prostaglandins) in tumour tissues, tissue remodelling and angiogenesis similar to that seen in chronic inflammatory responses, and tissue repair. These signs of 'smouldering' inflammation 2 are also present in tumours for which a firm causal relationship to inflammation has not been established (for example, breast tumours). Indeed, inflammatory cells and mediators are present in the microenvironment of most, if not all, tumours, irrespective of the trigger for development.Studies of genetically modified mice, adoptive-transfer experiments in mice, and analyses of human tumours have allowed researchers to begin to unravel the molecular pathways that link inflammation and cancer. Here we review current knowledge of the molecular and cellular pathways that link inflammation and cancer, and we describe how these pathways suppress effective antitumour immunity during tumour progression. We also discuss how cancer-related inflammation affects many aspects of malignancy, including the proliferation and survival of malignant cells, angiogenesis (which is required for the survival of cells within tumours of a certain size), tumour metastasis, and tumour response to chemotherapeutic drugs and hormones.Advances in understanding the genetic pathways involved in cancer have led to the development of a range of therapies that target malignant cells. Understanding the pathways involved in cancer-related inflammation could ...

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Section: The Big Questionsmentioning

confidence: 99%

Cancer-related inflammation

Mantovani

Allavena

Sica

et al. 2008

Nature

9,568

112

7,934

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“…To the best of our knowledge, only one melanoma patient was reported as a good responder to anti-TNF for several weeks. 8 Our preclinical findings may be of great interest in the clinic since we have identified high MHC-I expression by melanoma cells as a critical point to condition the antitumor effects triggered by the TNF blockade strategy. In addition, we document that TNF blockade was efficient only in immunocompetent animals.…”

Section: Introductionmentioning

confidence: 93%

Targeting TNF alpha as a novel strategy to enhance CD8⁺T cell-dependent immune response in melanoma?

et al. 2015

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“…A phase I clinical trial in patients displaying advanced cancer also resulted in lower IL-17 serum levels after Infliximab treatment (Table 1; refs. 8,9). Another TNF-a antagonist, Etanercept, which is a soluble p75 TNF receptor that inactivates TNF-a by competitive binding, was also assessed in phase I trials to evaluate its efficacy in treating recurrent ovarian cancer.…”

Section: Inflammatory Cytokine and Chemokine Network In Ovarian Cancermentioning

confidence: 99%

Revisiting the Complexity of the Ovarian Cancer Microenvironment—Clinical Implications for Treatment Strategies

Musrap

Diamandis

2012

Molecular Cancer Research

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Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies in North American women. Given that EOC encompasses a broad class of tumors consisting of a variety of different histologic and molecular subtypes, which generates genetically and etiologically distinct tumors, several challenges arise during treatment of patients with this disease. Overlaying this complexity is the contribution of supporting cells, particularly stromal components such as fibroblasts and immune infiltrates that collectively create a microenvironment that promotes and enhances cancer progression. A notable example is the induction of angiogenesis, which occurs through the secretion of pro-angiogenic factors by both tumor and tumor-associated cells. The recent development of angiogenic inhibitors targeting tumor vasculature, which have been shown to improve patient outcome when combined with standard therapy, has launched a paradigm shift on how cancer patients should be treated. It is evident that future clinical practices will focus on the incorporation of therapies that antagonize the protumoral effects of such microenvironment contributors. Herein, an overview of the varying tumor-host interactions that influence tumor behavior will be discussed, in addition to the recent efforts undertaken to target these interactions and their potential to revolutionize EOC patient care.

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A clinical study assessing the tolerability and biological effects of infliximab, a TNF-α inhibitor, in patients with advanced cancer

Abstract: Infliximab treatment was safe and well tolerated in patients with advanced cancer. There was evidence of biological activity with baseline TNF-alpha and CCL2 being correlated with infliximab response.

Cited by 157 publications

References 28 publications

Cancer-related inflammation

Cancer-related inflammation

Targeting TNF alpha as a novel strategy to enhance CD8⁺T cell-dependent immune response in melanoma?

Revisiting the Complexity of the Ovarian Cancer Microenvironment—Clinical Implications for Treatment Strategies

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A clinical study assessing the tolerability and biological effects of infliximab, a TNF-α inhibitor, in patients with advanced cancer

Abstract: Infliximab treatment was safe and well tolerated in patients with advanced cancer. There was evidence of biological activity with baseline TNF-alpha and CCL2 being correlated with infliximab response.

Cited by 157 publications

References 28 publications

Cancer-related inflammation

Cancer-related inflammation

Targeting TNF alpha as a novel strategy to enhance CD8+T cell-dependent immune response in melanoma?

Revisiting the Complexity of the Ovarian Cancer Microenvironment—Clinical Implications for Treatment Strategies

Contact Info

Product

Resources

About

Targeting TNF alpha as a novel strategy to enhance CD8⁺T cell-dependent immune response in melanoma?