Antibodies binding to an intracellular PRL-1 OR PRL-3 polypeptide
A PRL-1, antibody technology, applied in the medical field, can solve the problem that the antibody cannot pass through the cell membrane and cannot approach the antigen, etc.
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Embodiment 27
[0079] Example 27 shows that anti-PRL1 antibody 269 can bind to epitopes TYKNMR and TLNKFI. Accordingly, the present inventors provide anti-PRL antibodies such as anti-PRL1 antibodies that bind the sequence TYKNMR. The inventors also provide anti-PRL antibodies such as anti-PRL1 antibodies capable of binding TLNKFI. The anti-PRL antibody may have the ability to bind both sequences simultaneously.
[0080] Furthermore, Example 27 shows that anti-PRL3 antibodies can bind the epitopes KAKFYN and HTHKTR. Accordingly, the inventors provide anti-PRL antibodies such as anti-PRL3 antibodies that bind the sequence KAKFYN. The present inventors also provide anti-PRL antibodies such as anti-PRL3 antibodies capable of binding HTHKTR. The anti-PRL antibody may have the ability to bind both sequences simultaneously.
[0081] The anti-PRL antibody may comprise the variable region of antibody 269, the variable region of antibody 223 or the variable region of antibody 318, each of which is...
Embodiment 9
[0097] Example 9 describes the generation of PRL overexpressing tumors in mice and provides an animal model for metastasis and cancer therapy. Examples 10-12 demonstrate that animals treated with anti-PRL antibodies showed significantly lower metastatic lung tumors compared to animals not treated with anti-PRL antibodies. Specifically, the treated animals showed approximately 90% fewer tumors than untreated animals. The anti-PRL antibody is capable of binding and blocking the activity of a PRL polypeptide despite the intracellular localization of the PRL polypeptide. The inventors' studies represent the first demonstrations that metastasis can be effectively (approximately 90%) blocked by the use of monoclonal antibodies against the respective phosphatases despite their intracellular localization.
[0098] The present inventors have also shown that anti-PRL-3 monoclonal antibodies can effectively block the formation of metastases in the human ovarian cancer cell line A2780 ex...
Embodiment 1
[0445] Example 1. Cell lines: CHO-K1, A2780 and CT26
[0446] CHO-K1 cells, A2780 human ovarian cancer cells and CT26 mouse colon cancer cells were purchased from ATCC (Manassas, VA).
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