Chemotherapy, occasionally combined with radiotherapy, is a major method for treating lymphoma but frequently produces side-effects in patients. Thus, novel therapeutics should be developed as an alternative the chemotherapy in lymphoma patients. Although the cell adhesion molecule gicerins are almost entirely absent in most mature tissues, except for muscle and endothelial cells, various neoplastic cells strongly express gicerin in their cell membranes. This suggests the potential function of gicerin in the progression of tumors, including tumor growth, invasion and metastasis to distant organs from primary sites. In the present study, we assessed therapeutic effects of anti-gicerin antibodies on the murine lymphoma cell line YAC1. Gicerin was found to be expressed in the cell membrane of YAC1 cells and promoted the cell adhesion activity of the YAC1 cells on HUVECs, an endothelial cell line. In addition, YAC1 cells were implanted sub-cutaneously in mice in order to examine the therapeutic effects of anti-gicerin antibodies on lymphoma progression in vivo. The anti-gicerin antibodies suppressed and reduced the lymphoma tumor growth in the mice, whereas the growth of tumor mass was not inhibited by pre-immune IgG administrations. YAC1 cells were also implanted intravenously in mice in order to examine the effects of anti-gicerin antibodies on the pulmonary metastasis of lymphoma cells. The metastasis of the YAC1 cells to the lungs was inhibited by the injection of anti-gicerin antibodies. These findings indicate that anti-gicerin antibodies inhibit the progression of prednisolone-resistant lymphoma, making this a promising novel therapeutic method for treating refractory lymphoma cases.
The mother obviously recognizes the fetus as an antigen, and the fetus is protected from the maternal immunologic attacks by eliciting anti-alloreactive T cell antibodies (T lymphocytotoxic human fetal antibody; TLFA). TLFA contains several antibodies against the maternal cells. It is thus necessary for further understanding of TLFA to obtain a single antibody from EBV-transformed cord B cells. EBV-transformations were performed in 28 cord B cell samples, and 16 cell lines were established. Antibody-binding assays of the cloned fetal IgM antibodies were performed by the respective maternal T cells grown in secondary mixed lymphocyte culture (MLC) stimulated by the paternal non-T cells and the maternal long-term culture killer T cells (LCT) in three different families. There were two types of cloned antibodies as identified by their binding to the respective maternal MLC responding T cells and the LCT. Their functions were further analyzed by the maternal MLC and lymphocytotoxic assays by using maternal-paternal cell combinations from the three families. One type of antibody inhibited the maternal MLC T cell proliferation (% inhibition: up to 28.2%, p less than 0.01), and the other inhibited the killer activity of the maternal LCT (% inhibition: up to 45.2%, p less than 0.001). Such a fetomaternal interaction bears perhaps on the fundamental mechanism whereby the mother does not reject the fetus.
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