A humanized anti-IL-6 antibody (ALD518) in non-small cell lung cancer

Bayliss, Trevor J.; Smith, Jeff; Schuster, Michael W.; Dragnev, Konstantin H.; Rigas, James R.

doi:10.1517/14712598.2011.627850

Cited by 215 publications

(154 citation statements)

References 33 publications

(33 reference statements)

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“…In a mouse model, development of cancer-related anemia was prevented with the administration of rat antimouse IL-6 receptor antibody [25]. In humans, humanized anti-IL-6 antibody ameliorated lung cancer-related anemia and cachexia [26]. Therapy that blocks IL-6 might be effective for vasculitis and cancer-related symptoms in cases such as the present one.…”

Section: Discussionmentioning

confidence: 68%

AP-VAS 2012 case report: a case of ANCA-negative pauci-immune crescentic glomerulonephritis associated with IL-6-producing adenosquamous cell carcinoma of the lung

et al. 2013

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A 76-year-old man with lung cancer and multiple metastases was admitted for purpura and rapidly progressive glomerulonephritis. Adenosquamous cell carcinoma of the lung had been diagnosed 6 months earlier.Two anti-cancer drug regimens had no effect. At admission, his survival with his malignancy was estimated to be several months. Renal biopsy revealed pauci-immune necrotizing crescentic glomerulonephritis (CrGN). Negative results were obtained for myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA) and proteinase-3-ANCA by enzyme-linked immunosorbent assay, and for peripheral-ANCA and cytoplasmic-ANCA by indirect immunofluorescence. He was diagnosed with ANCA-negative pauciimmune CrGN. Although steroids were initiated, the patient died of renal failure and intestinal bleeding 2 weeks later. It was later found that cancer cells were positive for interleukin (IL)-6 and that serum IL-6 levels were significantly elevated, concomitantly with increased IL-8, granulocyte-colony stimulating factor and transforming growth factor-b levels. Some kinds of lung cancer are known to produce IL-6 that activate neutrophils and are related to ANCA-associated CrGN. It appears that IL-6 can activate neutrophils in the pathogenesis of ANCA-negative pauciimmune CrGN with lung cancer. Therapy that blocks IL-6 may prove to be effective in vasculitis and cancer-related symptoms in such cases.

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Section: Discussionmentioning

confidence: 68%

AP-VAS 2012 case report: a case of ANCA-negative pauci-immune crescentic glomerulonephritis associated with IL-6-producing adenosquamous cell carcinoma of the lung

et al. 2013

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“…Chaperones that promote protein folding are currently being developed for the treatment of Fabry's disease (Amicus Therapeutics), which results from misfolding of the enzyme α-galactosidase A, and antibodies targeting IL-6 are being tested for use in the treatment of non-small cell lung cancer. [49] Thus, therapies for OCA and vitiligo may now become a reality.…”

Section: Resultsmentioning

confidence: 99%

Biology and genetics of oculocutaneous albinism and vitiligo – common pigmentation disorders in southern Africa

et al. 2013

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The primary pigment that determines human skin, hair and eye colour is melanin, which is synthesised by melanocytes. Melanin protects the skin from ultraviolet (UV) radiation and there is an inverse correlation between the degree of constitutive pigmentation and the risk of sun-induced skin cancers. Besides the life-threatening cancer risk, loss of pigmentation results in premature aging, compromised cutaneous immunity and significant emotional distress to affected individuals. [1][2][3] During embryonic development, melanocyte precursors that arise from the neural crest populate several areas including the interfollicular epidermis and hair follicle bulge in the skin; the uveal tract of the eye; and the stria vascularis, vestibular apparatus and endolymphatic sac of the ear. The development of melanocytes is tightly regulated at the genetic level by a number of genes that control proliferation, survival and migration of precursor cells to the various sites of the body and their differentiation into active melanocytes. A key regulator of this process is the microphthalmia transcription factor (MITF), which has been dubbed the 'master regulator' of the melanocyte, capable of modulating expression of several melanocytespecific proteins.[4] MITF mutations result in Waardenburg syndrome type II.[5] Once the melanocyte has differentiated, MITF regulates expression of genes in response to UV exposure, facilitating the tanning response.Melanocytes produce two forms of melanin, black-brown eumelanin and red-yellow pheomelanin. Skin and hair colour Corresponding author: P Manga (prashiela.manga@nyumc.org)Pigmentation disorders span the genetic spectrum from single-gene autosomal recessive disorders such as oculocutaneous albinism (OCA), the autosomal dominant disorder piebaldism to X-linked ocular albinism and multifactorial vitiligo. OCA connotes a group of disorders that result in hypopigmented skin due to decreased melanin production in melanocytes and loss of visual acuity. There are four non-syndromic forms, OCA1-4, which are classified based on the gene that is mutated (tyrosinase, OCA2, tyrosinase-related protein 1 and SLC45A2, respectively). Despite the fact that multiple genes account for the various forms of OCA, the phenotypes of all four forms result from disruption in the maturation and trafficking of the enzyme tyrosinase. OCA2 is the most prevalent autosomal recessive disorder among southern African blacks, affecting 1/3 900 individuals; while OCA3, although rare, is most prevalent in southern Africa. Another common pigmentation disorder in southern Africa is vitiligo, which affects 1 -2% of people worldwide. Vitiligo is a complex, acquired disorder in which melanocytes are destroyed due to an autoimmune response. The aetiology underlying this disorder is poorly understood, although recent genetic association studies have begun to shed light on the contributing factors. Pigmentation disorders have significant psychosocial implications and co-morbidities, yet therapies are still lacking. Recent progress in...

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“…CRP levels also tended to reduction, while an apparent improvement of hand grip strength and fatigue was reported (Clarke et al, 2009). These preliminary results were confirmed by a phase II trial including non small cell lung cancer patients receiving the anti-IL-6 antibody at different doses (Bayliss et al, 2011). An anti-IL-6 receptor antibody is also available (Ohtori et al, 2012), however no data are shown in the literature about its effectiveness in both experimental and human cancer cachexia.…”

Section: Inhibition Of Cytokine Productionmentioning

confidence: 72%

Mechanism-Based Therapeutic Approaches to Cachexia

et al. 2013

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Cachexia is a multifactorial syndrome characterized by body weight loss, depletion of adipose tissue and skeletal muscle mass, and marked alterations of the metabolic homeostasis.The occurrence of cachexia significantly impinges on patient's morbidity and mortality, and on quality of life. Inflammation, anorexia/malnutrition, alterations of protein and lipid metabolism are among the main mechanisms involved in the development of cachexia. While anorexia and malnutrition are long known contributing factors, the mechanisms leading to inflammation and metabolic alterations were clarified later on. On these premises, several therapeutic approaches were proposed. Most of them are in the pre-clinical phase, but some already reached the clinical experimentation. The present review will focus on treatment options proposed on the basis of mechanistic alterations. In this regard, in addition to nutritional and anti-inflammatory strategies, also approaches based on perturbation of specific signal transduction pathways are taken into consideration.

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A humanized anti-IL-6 antibody (ALD518) in non-small cell lung cancer

Cited by 215 publications

References 33 publications

AP-VAS 2012 case report: a case of ANCA-negative pauci-immune crescentic glomerulonephritis associated with IL-6-producing adenosquamous cell carcinoma of the lung

AP-VAS 2012 case report: a case of ANCA-negative pauci-immune crescentic glomerulonephritis associated with IL-6-producing adenosquamous cell carcinoma of the lung

Biology and genetics of oculocutaneous albinism and vitiligo – common pigmentation disorders in southern Africa

Mechanism-Based Therapeutic Approaches to Cachexia

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