Supervisors info:
Δρ. Γαϊτανάκη Αικατερίνη, Καθηγήτρια Φυσιολογίας Ζώων (Μέλος ΔΕΠ) Τομέας Φυσιολογίας Ζώων & Ανθρώπου, Τμήμα Βιολογίας, Ε.Κ.Π.Α.
Δρ. Λυμπέρη Πηγή, Ερευνήτρια Α’, Διευθύντρια Ερευνών Εργαστήριο Ανοσολογίας, Τμήμα Ανοσολογίας, Ε.Ι.Π.
Δρ. Παπαζαφείρη Παναγιώτα, Αναπληρώτρια Καθηγήτρια Φυσιολογίας Ζώων Τομέας Φυσιολογίας Ζώων & Ανθρώπου, Τμήμα Βιολογίας, Ε.Κ.Π.Α.
Summary:
Natural antibodies (Naturally occurring Antibodies- NAbs) are antibodies present in the serum of healthy subjects without previous antigenic stimulation. NAbs have the ability to recognize self-and no self- antigens providing a surveillance system of the organism’s molecular state and confers to homeostasis, acting as a humoral element of innate immunity. Cell penetrating antibodies- CPAbs, a distinct subpopulation of NAbs, have the ability to penetrate living cells and accumulating in the cytoplasm or the nucleus. Polyreactivity seems to be directly related to the penetration ability of CPAbs and therefore they represent a potential pharmaceutical weapon against various diseases. More specifically the use of NAbs in cancer therapy has gained a lot of interest. Particularly, IgM- NAbs recognize specifically antigens on the surface of tumor cells called tumor-associated-carbohydrate-antigens (TACAs) and the polyreactive nature of these NAbs seems to play a major role in this recognition. The Immunology Laboratory of the Hellenic Pasteur Institute has been working on the characterization of natural antibodies, mostly on CPAbs subpopulation. In more detail, monoclonal natural CPAbs from BALB/c mice were isolated and the sub group of IgG- CPAbs was detected in the commercial preparation of intravenous immunoglobulin (IVIG). Latest studies, including the present one, were focused on the isolation of human monoclonal CPAbs from the sera of patients with plasma cell dyscarias (PCDs). In PCDs pathogenesis, a B cell clone starts randomly to over multiple itself, suppressing the others and resulting in the production of high levels of monoclonal Igs in the serum. In most cases, these mIgs are functional. Literature provides evidence that mIgs producing B-cell clones that have undergone malignancy may under physiological conditions produce NAbs. With this in mind, our labatory focused in the research of human monoclonal “natural” CPAbs derived from the sera of patients with PCDS. In this study, six (6) mIgGs from sera of patients with Multiple Myeloma and six (6) mIgMs from sera of patients with Waldenström’s macroglobulinemia were selected and isolated based on their ability to act as polyreactive antibodies. With the use of ELISA we identified their polyreactivity and examined their ability to penetrate into cancer cells (HeLa and MDA-MB-231) in vitro. Subsequently, we examined their biological function on the above human cancer cells, their ability to induce apoptosis and/ or cytotoxicity, and lastly their possible catalytic activities, by hydrolyzing nucleic acids. Our results validate that the isolated mIgs share common features with NAbs and indicate that some of them have the ability to penetrate living cells through energy- depended and/ or energy- independed manner. Our study on the biological effect of our isolated mAbs indicates that mIgGs induce mainly apoptosis on the cancer cells studied, whereas mIgMs showed a distinct cytotoxic effect. In conclusion, we demonstrate that sera of patients with PCDs represent an excellent source of natural antibodies, which can be exploited in a wide range of applications. Indeed, the multiple biological functions of NAbs make them a potential therapeutic tool in therapy and diagnosis of many disorders such as cancer. Natural CPAbs can be used for drug delivery, to deliver intracellular compounds with the desired biological activity, or they can be used in therapy per se as they express their own biological activities. Finally an innovative use of natural CPAbs could be their combinational use as carriers of biologically effective drugs, having together a desirable endogenous biological activity.
