Another hypothesis argues that streptokinase (produced by killed bacteria of species Streptococcus pyogenes together with plasminogen from the patient) is the active agent of Coley's toxins. This hypothesis is supported by the fact that streptokinase has been associated with successful treatment of thromboangiitis obliterans. Anti-angiogenesis In addition to the mechanisms above, Coley's toxins might be antiangiogenic – suppressing the formation of new blood vessels which are vital to the growth of tumors. However, angiogenesis is not a biochemical cause by itself but needs external triggers. Dendritic cells A robust fever, which occurs in response to Coley fluid, generates inflammatory factors with co-stimulatory activity, which activate resting dendritic cells (DC), leading to the activation of anergic T cells, possibly accomplished through a second process, where physical damage to cancer cells leads to a sudden supply of cancer antigens to the dendritic cell population. PAMP Recently (2008), an immunological explanation binding together immunological data with findings about spontaneous regression and epidemiological data indicating a lowered risk to develop cancer later after common infections, has been published. According to this hypothesis, pathogenic substances produced by bacteria, viruses, infectious fungi and other pathogens, but not human tissue, called 'pathogen associated molecular pattern' (PAMP) lead to activation and maturation of tumor-antigen loaded dendritic cells. One PAMP thought to play a major role is the unmethlyated CpG motif found in bacterial DNA. The CpG motif is recognized by toll-like receptor 9 (TLR9) and can induce a strong TH1 response. Availability MBVax Bioscience, a Canadian Biotech company, produces Coley Fluid for research and clinical study. A private biotech company, Coley Pharmaceutical Group, has conducted clinical trials using genetic sequences which may have contributed to Coley's toxin's effectiveness, and was acquired by Pfizer in January 2008. In addition, the Waisbren Clinic in Wisconsin reports they have used Coley's toxin to treat patients since 1972. Coley's toxins are generally not available where approval or licence is required (in particular in the United States and Germany). Drug makers including Pfizer and Sanofi-Aventis are interested in modern versions of Coley's toxins; Pfizer has acquired the Coley Pharmaceutical Group, set up in 1997 Germany Some specialized medical doctors in Germany apply Coley's toxins to patients. They can do so legally because, in Germany, unapproved medications may be produced, although they may not be sold or given away. Physicians can go to special laboratories and produce Coley's toxins there using their own hands.