Cytokine Storm

Cytokines are an integral part of the body’s immune system, but they also trigger adverse host responses such as fever, pain, and inflammation. “Cytokine storm” is a situation that the immune system produces excessive pro-inflammatory cytokines, locally or systemically, in response to a number of infectious and non-infectious stimulants, or physical and chemical damages. The high rate of patient death during the outbreak of severe acute respiratory syndrome (SARS), H1N1, and Ebola virus infection is a typical example of cytokine storm’s ferocity to negatively affect body functions. Currently, no antibiotics or antiviral drugs are able to stop the cytokine storm once it breaks out. At Anogen, we believe that tackling the harmful cytokine storm is a novel strategy of bio-defense.

We have initiated cytokine research since the 1990s and have developed hundreds of hybridomas that produce high specificity and high affinity monoclonal antibodies (mAbs) directed against many important cytokines, including TNF-α, GM-CSF, IL-2, IL-8, IL-10, IL-15, IL-17, IL-18, and TGF- β. In addition, three different ELISA kits for detection of multiple cytokine epitopes have been developed and widely applied to biomedical research.

Multiplex Human Cytokine ELISA Kit (Inflammatory)

Multiplex Human Cytokine ELISA Kit (M1/M2/MDSC Cytokines)

Multiplex Human Cytokine ELISA Kit (Th1/Th2/Th17)

Diseases with over production of cytokines:

In 2004, we developed humanized chimeric mAbs against chemokines IL-8 (CXCL8) and MCP-1 (CCL2) with specific neutralizing activity and gained multiple patents in the U.S, Europe, Canada, and China. The preclinical study of prevention and treatment of ARDS using a chimeric anti IL-8 Ab in the pre-clinical study were published on International Immunopharmacology: Humanized monoclonal antibody against the chemokine CXCL-8 (IL-8) effectively prevents acute lung injury.

We are currently developing diagnostic kits for clinical use to measure cytokine in patients. Combination of antibodies enable patient to receive individualized treatment according to specific cytokines involved.

ABCREAM: Anogen’s solution to psoriasis

IL-8 is a potent chemokine for neutrophils, growth factor of epidermal cells, and a pro-angiogenic factor. Psoriasis is a common skin disease characterized by scales that are built up with rapid growing keratinocytes accompanied by inflammation and redness around the scales. IL-8 levels elevate up to 150-fold in psoriatic tissue, suggesting its role in the pathogenesis.

Anogen-Yes Biotech is the first company utilizing anti IL-8 Ab to treat psoriasis. Our proprietary technology (ABCREAM) is a topical ointment containing IL-8 neutralization Ab. IL-8 neutralization Ab blocks the activity of IL-8 which mediates the abnormal proliferation and differentiation of keratinocytes, and increases neutrolphil infiltration in the lesion vicinity to exert the anti-inflammatory effect. The ointment was found to be effective during clinical trial. 49% to 53.8% of patients achieved a greater than 60% improvement and 12.9% to 15.3% of patients achieved a greater than 90% improvement in PASI scores after a six week treatment cycle with ABCream.

ABCream may be effective in treatment of other inflammatory skin conditions as well. Preliminary observations suggest that it may also be used for treatment of eczema, a common skin condition. It was awarded Class I New Drug Certificate issued by China Food and Drug Administration (CFDA) in 2001.


HFMD and IL-8

Hand, foot and mouth disease (HFMD) is a potentially life-threatening illness commmonly seen in children mostly younger than five years of age. HFMD associated with Enterovirus 71 (EV71) and Coxsackievirus A6 (CV-A6), members of the Picornaviridae family in the genus Enterovirus. Although present globally in most countries including Europe and North America, the largest HFMD outbreaks has been seen in the Asia-Pacific area, for unknown reasons. HFMD outbreaks are not only increased in recent years, but more severe cases are also more common. Even worse, the HFMD virus is likely to develop partial variations. The fatality rate of severe HFMD is higher.

Hyperglycemia, Pre-albumin and leukocytosis are currently used for clinical prediction of the severity of HFMD. However, they are both insensitive and nonspecific in HFMD patients.

It has been proved that cytokines and chemokines released by EV71 or CV-A6 infected immune cells contribute to the disease severity. The uncontrolled immune responses result in abnormally elevated expression of cytokines that cause inflammation, tissue damage, pulmonary edema and other pathological damage. This phenomenon is known as "Cytokine Storm".

It has been proved that cytokines and chemokines released by EV71 or CV-A6 infected immune cells contribute to the disease severity. The uncontrolled immune responses result in abnormally elevated expression of cytokines that cause inflammation, tissue damage, pulmonary edema and other pathological damage. This phenomenon is known as "Cytokine Storm".

The latest research showed that among many cytokines, IL-2, IL-4, IL-6, IL-8, IL-10, MCP-1, IFN-γ, GM-CSF and TNF-α increase in enterovirus infection. IL-8 is strongly associated with the severity of HFMD with massive neutrophil infiltration of tissue and organ. IL-6 and IL-10, although elevated in HFMD patients, are not related to the disease severity. Thus, IL-8 level could be used as a predictive marker in the early stages of severe enterovirus infection. In addition, humanized anti-IL-8 antibody may prevent fatal complications such as brainstem encephalitis (BE), and pulmonary edema (PE) to reduce the mortality of severe HFMD.

Our project is to develop a new medical device of multiplex cytokine immuno-assay (ELISA) for early prediction of severe HFMD and an effective therapeutic humanized antibody against IL-8.

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