Humanized anti-prostate stem cell antigen monoclonal antibody
Prostate stem cell antigen (PSCA) is expressed in the majority of prostate cancer patients, making it an ideal target for cancer immunotherapy. Murine monoclonal antibody 1G8 binds to PSCA with nanomolar affinity, but its efficacy as a therapeutic agent is limited by the generation of a HAMA response. The present invention discloses humanized 1G8 antibodies in which the majority of the mouse-derived epitopes have been removed. These humanized antibodies bind PSCA with high affinity and specificity, and have been shown to reduce human bladder tumor take in a nude mouse model. These characteristics make the humanized antibodies of the present invention attractive agents for the treatment and detection of tumors expressing PSCA.
1. A humanized antibody comprising:
a) a light chain variable region comprising the amino acid sequence of SEQ ID NO:7 and
b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:9,
wherein said humanized antibody binds prostate stem cell antigen (PSCA), and wherein administration of said humanized antibody to a subject diagnosed with prostate cancer decreases tumor growth to a greater extent than treatment with the murine 1G8 monoclonal antibody produced by the hybridoma deposited as ATCC No. HB-12612.
2. The humanized antibody of claim 1 , wherein said antibody has an affinity constant for prostate stem cell antigen (PSCA) of at least about 2.5×10 8 .
3. The humanized antibody of claim 1 , further comprising a conjugate.
4. The humanized antibody of claim 3 , wherein said conjugate is selected from the group consisting of a toxin, a cytokine, a chemotherapeutic agent, and a radiolabel.