NATURAL HUMAN MONOCLONAL IGGS ARE ABLE TO PENETRATE METASTATIC BREAST CANCER CELLS AND PRESENT ANTI-NEOPLASTIC EFFECTS ON CANCER CELL MIGRATION AND VIABILITY
- Theodora Stivarou, Greece
Abstract
Background and Aims
Our laboratory has previously studied human, polyclonal, Natural Antibodies (NAbs) endowed with polyreactivity and cell-penetrating capacity in Intravenous Immunoglobulin therapeutic preparations. Recently, our interest has been focused on human monoclonal IgGs (mIgGs) endowed with Cell-Penetrating ability (CPAbs). In particular, we aimed to analyze CPAbs potential anti-neoplastic biological activities in metastatic breast cancer cells.
Methods
A series of mIgGs from Multiple Myeloma-G patients sera (known to contain high concentration of mIgGs exhibiting frequently NAb-like properties) were isolated by protein-G chromatography. The purity and monoclonality of mIgGs were verified by SDS-PAGE and IEF, respectively, while their polyreactivity against self- and non-self- antigens, by ELISA. mIgGs cell-penetrating capacity was analyzed in MDA-MB-231 metastatic breast cancer cells by immunofluorescence experiments and their effect on apoptosis and cancer cell migration, by flow cytometry and wound healing assays, respectively.
Results
Among 41 purified human mIgGs, 19 had cell-penetrating capacity with distinct cytoplasmic staining patterns. Three CPAbs inhibited MDA-MB-231 cell migration and also induced apoptosis. Moreover, two other CPAbs, which enhanced MDA-MB-231 motility, had no effect on their viability likewise to four CPAbs and three mIgGs without cell-penetrating capacity which also had no effect nor on cellular migration or cell viability.
Conclusions
We provide evidence that human natural mIgGs with cell-penetrating capacity exhibit anti-neoplastic functions and could be exploited as advantageous -due to their natural origin- anti-neoplastic tools. In conclusion, we consider that CPAbs could be used in cancer immunotherapy either per se, or as carriers for intracellular drug delivery, or both.