Abstract

BackgroundVarious immunotherapeutic approaches have been used for the treatment of cancer. A number of natural compounds are designed to repair, stimulate, or enhance the immune system response. Among them are the hemocyanins (Hcs) - extracellular copper proteins isolated from different arthropod and mollusc species. Hcs are oxygen transporter molecules and normally are freely dissolved in the hemolymph of these animals. Hemocyanins are very promising class of anti-cancer therapeutics due to their immunogenic properties and the absence of toxicity or side effects. KLH (Megathura crenulata hemocyanin) is the most studied molecule of this group setting a standard for natural carrier protein for small molecules and has been used in anti-tumor clinical trials.ResultsThe Hcs isolated from marine snail Rapana thomasiana (RtH) and the terrestrial snail Helix pomatia (HpH) express strong in vivo anti-cancer and anti-proliferative effects in the developed by us murine model of colon carcinoma. The immunization with RtH and HpH prolonged the survival of treated animals, improve humoral anti-cancer response and moderate the manifestation of C-26 carcinoma symptoms as tumor growth, splenomegaly and lung metastasis appearance.ConclusionHemocyanins are used so far for therapy of superficial bladder cancer and murine melanoma models. Our findings demonstrate a potential anti-cancer effect of hemocyanins on a murine model of colon carcinoma suggesting their use for immunotherapy of different types of cancer.

Highlights

  • Various immunotherapeutic approaches have been used for the treatment of cancer

  • Molecules of molluscan Hcs are structured as decamers or didecamers of subunits with molecular mass of 350–450 kDa

  • These results suggest the presence of crossreactive epitopes within the hemocyanins and C-26 colon carcinoma cells

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Summary

Introduction

Various immunotherapeutic approaches have been used for the treatment of cancer. Hemocyanins are very promising class of anti-cancer therapeutics due to their immunogenic properties and the absence of toxicity or side effects. KLH (Megathura crenulata hemocyanin) is the most studied molecule of this group setting a standard for natural carrier protein for small molecules and has been used in anti-tumor clinical trials. Each type of cancer requires specific treatment, which explains the need for development of highly specific targeted anti-cancer agents [1]. In the last years a number of therapeutic antibodies have been approved for clinical treatment in cases of breast cancer (Trastuzumab), non-Hodgkin (Rituximab) and Hodgkin lymphoma (Brentuximab vedotin), colorectal cancer (Panitumumab, Cetuximab), chronic lymphocyte leukemia (Alemtuzumab), and acute myelogenous leukemia (Gemtuzumab ozogamicin) [4]. IL-2 in metastatic melanoma and renal cell carcinoma and IFN-alpha in Stage III melanoma have been permitted for cancer therapy [5]

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