Immunokines

What are Immunokines?

An old name for cytokines. Immunokine became also a trademark for WF10.

What is WF10?

WF 10 [TCDO, Oxoferin, Immunokine, Macrokine] is a 1:10 dilution of tetrachlorodecaoxide formulated for IV delivery. It was developed by Oxo Chemie in Switzerland as an adjunctive therapy to combination antiretroviral and opportunistic infection prophylaxis regimens in AIDS patients. WF 10 specifically targets macrophages. Oxo Chemie has worldwide patent rights to WF 10 and Dimethaid Research has an exclusive licence for marketing and distribution in Canada. In May 2002, Oxo Chemie was acquired by Dimethaid Research. Oxo completed a trial in 72 cervical cancer patients undergoing radiation therapy in 1989. Results from this trial demonstrated complete remission in 75% of patients receiving WF 10. A follow-up placebo controlled trial in 1996 produced similar results. WF 10 has received regulatory approval in Thailand for postradiation cystitis following a trial completed in 1998 in 20 patients following radiation treatment for cervical carcinoma. This authorisation also allows limited availability of WF 10 at the physician’s request in Germany. WF 10 is also available under Health Canada’s Special Access Program. Oxo Chemie has completed a controlled randomised, crossover study in France in 1991 that examined the effects of 103 patients with acute radiation dermatitis and radiation- or chemotherapy-induced mucositis. Results demonstrated that WF 10 significantly improved lesions and accelerated recovery without side effects. Topical tetrachlorodecaoxide in a less concentrated formulation (1:55) is marketed in many countries as Oxoferin for wound healing. WF 10 is approved for use in Thailand under the name IMMUNOKINE in patients with postradiation chronic inflammatory disease including cystitis, proctitis and mucositis. In July 2003, the European examiners informed Oxo Chemie that they intend to grant the company additional patents to the technology platform that supports WF 10, extending the European protection granted in 1992 to cover a much broader range of diseases. The patents will be granted in Austria, Belgium, Cyprus, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Liechtenstein, Luxembourg, Monaco, the Netherlands, Portugal, Spain, Sweden, Switzerland and the UK. Patent claims cover potential treatment for autoimmune disease, organ transplant or graft rejection, lymphoma and inflammation manifested as hepatitis or chronic obstructive pulmonary disease.

The function of Immunokines

The tumor may arise in the dysregulation of the immune system, which plays pivotal roles in counteracting tumor colonization, late-stage tumors, and metastases.

In the middle of the institution of cancer in vivo, immune cells are triggered to release a great number of immunokines, like cytokines, and chemokines.

Signalling in Cancer

Therefore, since cytokine levels in tumor-bearing host would be differential among local (intratumoral lesion, peritumoral ordinary tissue), and systemic evaluation website (serum), those differences may be significantly related to prognosis and treatment results for cancer sufferers. Previously, despite the few of patients, we demonstrated the feasibility of the proposition via just profiling. Based on this, herein we suggest that profiling would be utilized as progression, and a predictive tool for cancer staging.

In vivo and in vitro techniques are utilized to analyze the influence of different immunokines on the HPA axis and to ascertain if their activities are modulated by glucocorticoids and lipocortin 1 (LC1). We previously reported on the recruitment of CD11b+ leukocytes because of tumor site-specific enrichment of TNF activity after intravenous administration of a dimeric TNF immunokine with specificity for fibroblast activation protein (FAP).

However, extravasation and TNF-induced chemo-attraction of PMNs from bloodstream to the tumor is a multistep process essentially mediated by interleukin 8. With the aim to enhance the TNF-induced and IL-8-mediated chemotactic response, we created immunocytokines by N-terminal fusion of an individual anti-FAP scFv fragment with individual IL-8 (IL-8(72)) and its own N-terminally truncated form IL-8(3-72)The aggressiveness of melanoma is believed to be correlated with tumor-stroma-associated immune cells.

Cytokines and then modulate the actions of those cells, ultimately affecting disease development and chemokines act to recruit. Because melanoma often metastasizes to the mind, we asked whether global differences in immunokine profiles can be detected in the cerebrospinal fluid (CSF) of melanoma patients and reveal aspects of tumor biology that correlate with patient results.

Cytokine involvment in Melanoma

We measured the levels of 12 chemokines and 12 cytokines in melanoma individual CSF and the data were analyzed to develop heat maps and hierarchical cluster grams. Unexpectedly, the overall profiles of immunokines found in these samples showed a generalized reconfiguration in the expression in melanoma patient CSF, resulting in the segregation of individuals

Implication of immunokine profiling for cancer staging.
Immunokine profiling in mouse skin and serum lysates showed a decline in the proinflammatory response in the shungite-treated groups. The redox profile of shungite-treated groups showed counterbalance of ROS/RNS and superoxide levels in serum and skin lysates.

Last, we have confirmed the involvement of Nrf2- and MAPK-mediated oxidative stress pathways from the antioxidant mechanism of shungite.