The etiology and pathogenesis of ovarian cancer are still not fully understood. None of the so far proposed hypothesis on the development of OET can fully account for the epidemiologic and clinical findings in the context of reproductive factors and OET development. Further research approaches are warranted and need to put more weight on the clinical and genetical diversity of OET to yield a more detailed insight into their pathogenesis.
Humanized tumor mice (HTM) were generated by the co-transplantation of human hematopoietic stem cells and human breast cancer cells overexpressing HER2 into neonatal NOD-scid IL2Rγ(null) (NSG) mice. These mice are characterized by the development of a human immune system in combination with human breast cancer growth. Due to concurrent transplantation into newborn mice, transfer of MHC-mismatched tumor cells resulted in solid coexistence and immune cell activation (CD4(+) T cells, natural killer cells, and myeloid cells), but without evidence for rejection. Histological staining of the spleen of HTM revealed co-localization of human antigen-presenting cells together with human T and B cells allowing MHC-dependent interaction, and thereby the generation of T cell-dependent antibody production. Here, we investigated the capability of these mice to generate human tumor-specific antibodies and correlated immunoglobulin titers with tumor outgrowth. We found detectable IgM and also IgG amounts in the serum of HTM, which apparently controlled tumor development when IgG serum concentrations were above 10 µg/ml. Western blot analyses revealed that the tumor-specific antibodies generated in HTM did not recognize HER2/neu antigens, but different, possibly relevant antigens for breast cancer therapy. In conclusion, HTM offer a novel approach to generate complete human monoclonal antibodies that do not require further genetic manipulation (e. g., humanization) for a potential application in humans. In addition, efficacy and safety of the generated antibodies can be tested in the same mouse model under human-like conditions. This might be of particular interest for cancer subtypes with no currently available antibody therapy.
Ovarian epithelial cancer (OEC) is the most lethal gynaecological malignancy
and the sixth most common cancer among women in industrialised countries.
This review summarises the current knowledge on the role of reproductive
factors for the development of OEC. Recent studies have shown that OECs
represent a diverse group of cancers. This is partly reflected in the
results of epidemiological and clinical studies which have investigated the
impact of various reproductive factors on the risk of developing OEC. Fewer
ovulatory cycles, parity and lactation were found to decrease the risk for
OEC, whereas the association between infertility and ovarian cancer has not
yet been fully elucidated and further investigation is required. None of the
proposed hypotheses on the development of ovarian cancer fully explains the
epidemiological and clinical findings of the association between
reproductive factors and OEC development. Further research is warranted
which would focus more on the clinical and genetic diversity of OECs to
obtain a better understanding of the pathogenesis.
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