Monoclonal antibodies

//Monoclonal antibodies
Monoclonal antibodies 2017-10-19T10:44:51+00:00

Dr. Bander’s opening remark was that it is prostate cancer outside of the prostate that kills us, and there is no known cure for such cancer. He then told us about his work with the Monoclonal antibodies (MAb). He is working with an MAb that is specific to Prostate Specific Membrane Antigen (PSMA) and has been cloned to make a large number of them. He is using the hu J591 which is a humanized antibody as opposed to the original mouse antibody. By using the humanized antibody he is avoiding the immune reaction that can occur with the mouse antibody. The ProstaScint test is using the mouse antibody.

All cells produce molecules that are expressed on their surface. Cancer cells will express some of the same molecules, but also others that mark them as cancer. In prostate cancer cells this molecule is PSMA. The more aggressive the prostate cancer is the more PSMA it will show on its surface. The MAb is specific to PSMA and will bind to it wherever it finds the PSMA. When I heard him talk in New York on 10 September he told us that others cells make PSMA, but it is not expressed on the outside of the cell and thus is not available to the antibody.
These monoclonal antibodies can be used in several ways as follows:

w Naked with nothing attached to them. In this way they can be used to attract the bodies defenses to the cancer cells.
w With a radioactive agent attached. In this way they can be used as a tracing agent, think ProstaScint, or they can deliver a lethal dose of radiation to the cancer cells.
w With a chemotherapy agent attached. This will get the therapeutic agent directly to the cancer cells and leave the normal cells alone.
w With a drug attached. This will put the drug in the presence of the cancer and away from the normal cells.

Dr. Bander told us that he had 14 patients in a phase I study of the naked monoclonal antibody. This was a test to ascertain the tumor targeting ability of the antibody which he said was shown to be very good, and there was no toxicity or allergic reactions.
In his study of hu J501 plus Interleukin 2 Dr. Bander has 4 patients enrolled and it is too early to get any data from this study.

Dr. Bander is doing a study of the MAb with Itrium 90 attached. He has 20 patients enrolled in this one. In another study with 6 patients enrolled he is studying the MAb with Luticium 177 attached. He said that he is getting a very good dose related response and he showed us a slide with 4 dose escalation’s represented. At dose level 1 the PSA rate of rise started to decline. At dose level 2 the PSA leveled off and flattened out. At dose level 3 you could se a bit of decline in PSA and dose level 4 showed a steep decline.

He is not seeing any toxicity and the metastasis in the lymph nodes of 2 patients disappeared. He will be completing this phase I trial in about 2 more months and then will go to phase II. He believes that he will gain FDA approval in about 4 years. Dr. Bander told us that the FDA does not accept PSA as an indication of effectiveness in a study, but they have to see measurable results on the tumor itself. Dr. Bander said that men may receive repeat doses of hu MAbs with no allergic reaction.