Hemocyanine / KLH
biosyn is a world leader in the manufacture of high quality, clinical / GMP and research grade hemocyanin products (IMMUCOTHEL® and VACMUNE® liquid) derived from the hemolymph of the sea snail, Meghathura crenulata, also commonly known as the Giant Keyhole Limpet. The hemocyanin derived from this snail is widely known as Keyhole Limpet Hemocyanin, in short KLH.
IMMUCOTHEL® – for recurrence prevention of superficial urinary bladder carcinomas
Superficial bladder cancer: Instillation therapy with IMMUCOTHEL® for recurrence prevention
Bladder cancer is the second most common malignancy of the urogenital tract and the fourth most common type of cancer in men. The standard treatment for preventing post-TUR recurrences has been instillation therapy with cytostatics and/or the immunotherapeutic agent BCG. Both are associated with good efficacy, but also with certain side effects. The availability of BCG is currently limited.
IMMUCOTHEL® is a well-tolerated and efficacious immunotherapeutic agent for instillation therapy to prevent recurrences of superficial bladder cancer. Its benefits lie in the fact that its efficacy is equipotent to chemo- or immunotherapy with BCG but has markedly fewer side effects.
Compared with BCG and Mitomycin, IMMUCOTHEL® shows the lowest therapy failure rate (1%), a 10 times lower side effect rate (5%), 0% allergic reactions and a 17% five-year disease-free survival rate. Details on recurrence prevention in superficial urinary bladder carcinomas below:
IMMUCOTHEL®: Significant extension of the recurrence-free interval
The most frequent variant of KLH consists of 20 subunits that form two connected rings (didecamers) with a molecular weight of about 8 million Dalton. The dissociated subunits of KLH form the immunocyanin with a molecular weight of about 400 KiloDalton.
If one administers immunocyanin to patients, this results in the body's confrontation with hundreds of xenogenic epitopes of this molecule and triggers the activation of the patient's immune system. The protein structures of the immunocyanins induce increased activation or synthetization of T-helper cells, cytotoxic T-suppressor cells, IFN-α, IFN-γ, IL-1a, and IL-2, macrophages and NK cells are stimulated. For patients with superficial urinary bladder carcinoma, the recurrence-free interval is significantly (≥ 100%) extended by KLH (IMMUCOTHEL®) (Fig. 1).
KLH: Mechanism of action
- KLH stimulates the immune system
- KLH has a direct cytotoxic effect
- Strong KLH immunogenicity is based on the attached oligosaccharides
The exact mechanism of action of KLH is not yet known. KLH itself shows moderate anti-carcinogenic activity . However, the effect of KLH on superficial bladder carcinomas is based on its capability of stimulating the immune system  (Fig. 1).
The strong immunogenicity of KLH is probably based on the numerous attached oligosaccharides that account for about 4% of the molecular mass of KLH  (Fig. 2).
Different mechanisms of action play a role here: on the one hand a non-specific stimulation of the immune system , and on the other hand the stimulation of cytotoxic T-cells. The third mechanism of action is the induction of antitumoral antibodies.
After an immunization with KLH, mice produced antibodies that bind tumor-associated oligosaccharide antigens . In addition, studies with bladder carcinoma patients showed an increase of anti-KLH antibodies in patients who responded to KLH treatment .
An additional study showed that KLH expressed Gal(beta 1-3) GalNAc-bearing oligosaccharides. The immunization of rats with KLH induces the production of anti-Gal(beta 1-3)Gal-NAc antibodies. Since bladder carcinomas express cross-reactive Gal(beta 1-3)GalNAc epitopes (also called Thomsen-Friedenreich antigens), the effectiveness of immunotherapy with KLH for superficial bladder carcinoma is most likely based on this fact .
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