Natural antibodies and cancer

Abstract

The innate or natural immunity is the basis and key for all immune processes. Specific receptors on macrophages, dendrites, NK cells and natural antibodies producing B cells act as a first line defense and remove all 'foreign' and potentially harmful substances, that is, bacteria, viruses, cellular waste, modified molecules and, most importantly, cancer cells. Recognition and removal of transformed cells is a lifelong task of immune surveillance processes. Antibodies are hallmark components of this anti-cancer activity. To investigate their nature, specificity, and function, we used the human hybridoma technology for isolating antibodies from cancer patients. These were then tested with a panel of assays against cancer cell lines in vitro and in vivo. Interestingly, all the tumor-specific antibodies we found were germ-line coded and belonged nearly exclusively to the IgM class. Furthermore, they all bound to new carbohydrates on post-translationally modified cell surface receptors on malignant cells. So far no affinity maturated immunoglobulins detecting tumor-specific peptides were found. However, only the presentation of peptide motifs can create an immunological memory. In general malignant cells are detected at very early precursor stages and manifest tumors can be considered as exceptional events. In addition, malignant cells are neither infectious nor hide intracellularly like viruses and some bacteria. Therefore, it makes sense that anti-tumor immunity seems to be solely a part of the natural immunity and a memory is not needed and therefore not induced. This indicates that the tumor immunity seems to be restricted to innate immune mechanisms and the instruments used by nature, like natural antibodies, are obviously excellent therapeutics.

The non-inflammatory role of C1q during Her2/neu-driven mammary carcinogenesis

“…The data obtained demonstrated that the loss of C3 activation, whose fragments were found to specifically accumulate in vessels and stroma in and around the incipient cancers, was responsible for the dramatic increase in the aggressiveness of neu C mammary tumors. Concomitantly, as had already been demonstrated in cancer patients, 32,33,34 spontaneous antitumor antibodies increased in neuT mice during the course of tumor progression. 24 Taken together, these observations suggest that the complement system can take on a tumor-inhibiting role that is played out through the activation of the classical pathway.…”

Characterization of an immunodominant cancer-specific O-glycopeptide epitope in murine podoplanin (OTS8)

“…Glycosylation may also modulate protein processing and hence affect exposure of new epitopes as shown in Rasmussen's encephalitis, where an N-glycan blocks proteolysis of a neuronal glutamate receptor and the establishment of a short peptide epitope [40]. Several human monoclonal antibodies have been shown to be directed to epitopes affected by glycosylation [41][42][43][44][45] but it is currently unclear if these antibodies define glycopeptide epitopes per se. The O-glycopeptide autoantibody epitopes identified on human MUC1 and murine podoplanin are therefore important models for this type of epitope.…”

The Catastrophic Antiphospholipid Syndrome in Serbia: Diagnostic and Management Problems

“…This is beyond the scope of this review but we note this literature. It would certainly be literature that Dr. Ron Asherson would have enjoyed reading [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37].…”