A Precision Strike to Treat Prostate Cancer

By Jim Stallard,

Graphic of antibody binding to a protein
Summary

Current prostate cancer drugs often lose their effectiveness over time. A new approach involves using an antibody to deliver toxic radioactive particles selectively to prostate cancer cells.

There are many effective prostate cancer drugs, but a major challenge is that they often stop working. One common treatment, hormone therapy, is initially effective at blocking the cancer-fueling effects of testosterone. But these drugs can lose their power as the prostate cancer evolves.

Researchers have looked for better ways to target prostate cancer cells and monitor whether treatments are working or the cancer is progressing. In 2016, promising news emerged from the laboratory of Steven Larson in the Sloan Kettering Institute of Memorial Sloan Kettering. Scientists demonstrated that an antibody called hu11B6 binds to a protein, called hK2, which is secreted only by prostate cells.

In that study, the researchers tested this technology for diagnostic purposes, proving in mice that they could track prostate cancer spread and determine when hormone therapy was no longer working. Now these same researchers report that this approach can be used to deliver drugs to prostate cancer cells without destroying nearby healthy cells.

This therapy offers the possibility of exclusively targeting prostate cancer cells and represents a potential improvement in diagnosis, staging, and treatment.
Hans David Ulmert
Hans David Ulmert molecular pharmacologist

By linking hu11B6 to a radioactive particle called actinium-225, they showed they could deliver a precision strike to the prostate cancer cells. In mice, a single dose of the drug wiped out prostate cancer and caused the animals to live significantly longer. The researchers further showed that hu11B6 is efficient in nonhuman primates. The distribution of hu11B6 — how it moves from the bloodstream into the body’s tissues — is the same whether carrying a diagnostic particle or a toxic warhead such as actinium-225. This makes it possible to plan the minimal dose needed to treat a patient.

The method is reported today in the journal Nature Communications by molecular pharmacologist Hans David Ulmert and radiochemist Michael McDevitt, along with other researchers at MSK and several other institutions.

“Unlike radiation or chemotherapy, this therapy offers the possibility of exclusively targeting prostate cancer cells and represents a potential improvement in diagnosis, staging, and treatment,” Dr. Ulmert says. “Because we can choose which radionuclide to attach to hu11B6, we have exquisite control over the lethality of the drug and its risk to patients.”

Enlarging the Target

One advantage of this therapeutic approach is that, in effect, it makes the target more abundant as it works. Production of hK2 is regulated by a protein called an androgen receptor, which plays a central role in driving prostate cancer. When the radiolabeled antibody is drawn into the cell by binding to hK2, the cells are either immediately wiped out, or repair mechanisms in the cells set off a cascade of events that makes the androgen receptor more active. This in turn boosts hK2 production, giving the drug even more hK2 to home in on.

The research team was recently awarded the Impact Award by the Department of Defense to develop and evaluate non-invasive imaging technologies to assess this radiobiological phenomenon.

Dr. Ulmert is optimistic that this technology could enter human testing soon. A humanized form of the hu11B6 antibody has already proved to be safe in nonhuman primates. A clinical trial is currently being planned that will be led by medical oncologist Michael Morris and conducted at MSK.

“This could launch a wave of new antibody-based drugs targeting the hK2 protein,” Dr. Ulmert says. “Given that a single injection could eradicate the cancer, it strongly suggests we are hitting the right target. If we are successful at using this approach to deliver drugs in humans, it could change the course of the disease.”

This study was supported in part by the Imaging and Radiation Sciences Program 563 (IMRAS), US National Institutes of Health (NIH) grants P30 CA008748 (MSK Cancer Center Support 564 Grant) and P30 CA006973 (Johns Hopkins University Cancer Center Support Grant).

Comments

This is an amazing event! Do any prescription medicines used to treat BPH, such as Avodart, or Cialis, have any negative effects upon the results? I am very interested.

Art, thank you for reaching out. This research has not yet entered human testing, so it is unknown at this point if these prescription medicines would affect the results. However, you can check back on the research at this site, and if you are interested in participating in a clinical trial at MSK, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment.

I'm very interested in this treatment. I would love to participate in any trial using this new approach. Do you think this might be possible?

I realize that use in humans is years away, but this is exciting news! As a prostate cancer survivor, I'm curious to know if this type of treatment might be regarded as allowable for a patient that had previously undergone radiation therapy to treat recurrent cancer. In my case, I underwent a radical prostatectomy in 2004, and a series of 38 radiation therapy sessions in 2010 when the cancer reappeared. I've been blessed to see my PSA level fall to 0.46 and then to 0.3 after climbing to 0.6 about a year ago. If the cancer does return again, my only option appears to be the hormone therapy mentioned in the article. I'd be delighted to have such a targeted therapy available to me.

I had seeds for prostate cancer 16 yearsago, my urologist can not do a cystoscopy in his office, he wants to do this in a hiospital setting, should I get a second opinion?

Hello,
I am a 5 year survivor following a radical prostatectomy and salvage radiation of my lymph nodes. I am on my 5th year of lupron. I am very interested in participating in your study once it becomes available to human subjects. Thank you

Had radical prostatectomy December 2015, learned PSA exploded to 1.4 in September 2018. Was injected with Lupren last week, am scheduled for 40 radiation appts over eight weeks starting December 19 2018. Meeting with urologist Oct. 30 2018. Based on what I've read so far, I'm very interested in learning more about MSK-impact and possibly participating in trials. Please advise.

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