Antibody for PSMA - what's the problem?

Why is there not an antibody for PSMA? This would conceptually kill prostate cells in the blood stream. That would be awesome!

[AlanMeyer]

There is a known antibody "(1)(7)(7)Lu‐DOTAhuJ591 anti prostate specific membrane antigen specific monoclonal antibody".

See: ncbi.nlm.nih.gov/pubmed/257... for some information about its use in PCa treatment.

See: ncbi.nlm.nih.gov/pmc/articl... for info about binding the antibody to a radioactive atom (Lutetium 177) which is in clinical trials in the U.S. and is available, outside of trials I think, in Germany. There was a posting here about this earlier.

It looks like it's not a cure. To begin with, not every tumor cell in most patients has PSMA on its surface. However it does appear to have promise as another treatment - one that is not related to ADT or chemo and might work when others don't.

Alan

[Hidden in reply to AlanMeyer]

The Lutium 177 and DOTA mentioned in the pubmed article echoed something I heard at the neuroendorine (tumor) [NET] regional conference in Buffalo. May be the same/similar payload but different targeting? J591 is the mab for targeting!

Hey, here is an awesome trial. It's an administration of J591 (just once however) but with an alph emitter attached (Actinium225) to kill. Not yet recruiting.

NYC/Weil clinicaltrials.gov/ct2/show...

Leutium 177 is not an alpha emitter, must be a beta emitter. More collateral damage.

I wonder if this means that PRRT might be getting AC225 as the isotope!! Cool. But odds are, not.

[AlanMeyer in reply to Hidden]

I looked at the trial you cited and, once again, I was impressed by how complex advanced cancer research is. Sometimes it makes rocket science look like kid stuff by comparison.

[podsart in reply to AlanMeyer]

AlanMyer

These references are great, thanks

The article says: "Those men with progressive disease who do not respond to 177Lu PSMA therapy range from 10% to 32%." also that the PSMA expression increases with Gleason score. The weakest impact seems to be for heavy bone mets

Again the tests are for those with end stage disease. This doesn't tell us how well works with low Pca burdens. Visceral tissue metastasis I thought to be especially difficult, especially tough in certain difficult areas for treatment, so a combined therapy of bone mets with PSMA or some other strategy could be interesting

Given the extremely hostile tumor environment to therapy where immune therapy, I hear, has tough time penetrating, PSMA seems great . Those with low volume disease might have much higher success rates.

Am I seeing this incorrectly?

[AlanMeyer in reply to podsart]

podsart asked: "Am I seeing this incorrectly?"

Until I've finished three books on biochemistry, three on molecular biology, four on cancer medicine, and have completed 20 years of lab research, I'll put off answering your question :^).

Or to answer your question more succinctly I'll just say, "Damned if I know!"

Alan

[wrando]

prostatecancernewstoday.com...

Interesting link

[cesanon]

The reason there is not an antibody for PSMA is that there needs to be a funded clinical study.

If anyone has a good candidate for such a study, it would be a reasonable lift to fund it as an orphan drug clinical trial with round of small investments from prostate cancer patients.

The legal part of it is not so hard with the recent implementation of regulation cf raises. I could do that part.

Anyone else want to volunteer for some of the other parts?

[Hidden in reply to cesanon]

au contraire. making one is simple. they apparently have and tested it (in 2013). Dan Petrylak. ascopubs.org/doi/abs/10.120...

clinicaltrials.gov/show/NCT...

no results posted.

[cesanon in reply to Hidden]

"no results posted."

Oops sorry, I mean no successful clinical trial. LOL

It has to work. Then it has to be commercialized...

This is a phase 1 trial. It's purpose is to identify early problems.

That particular drug is not listed in their pipeline of potential drugs:

progenics.com/product-pipel...

[AlanLawrenson]

Just to give you my ten cents worth, my brother aged 77, with mCRPC, recent underwent PSMA Lu-177 treatment in Sydney, Australia. He had two injections over about 7 weeks. His original PET scan showed about 50 mets around his body. His PSA was about 9 before the injections. His Gleason was 9. He had been on ADT for two years and Xtandi for a year. Also a strict diet and a reasonable exercise routine.

Results after the two injections: PSA down to 1.24 ; Pet scan shows only one very small met. His bone pain is gone. He has stopped all other treatment. His kidney function has improved (blocked by cancerous ureter). He is having follow up PSA this week. He is likely to have further PET scan in four months time. More details on my ProstateTalk newsletter at anabcofprostatecancer.com.au.

Wrando's article reference was excellent. Shows whats happening.

[cesanon]

I just asked Dr. Myers about PSMA Lu-177 treatment.

He says he has several Australian patients who have had the treatment. He thinks it may now be available in New York where it was first invented.

But he is dubious about its effectiveness. So far it's effect seems to be temporary... with remissions in about a year or so.

Currently he thinks that (other than ADT) Zytiga and Xofigo are the two most effective medications for prostate cancer metastasis. And Xtandi isn't so impressive.

[Hidden in reply to cesanon]

So Abiratirone, and Radium, with Enzalutimide being not so impressive.

PSMA Lu-177 is a beta emitter, so dose limited by collateral damage. There is some thought the J591(PSMA antibody)+ "alpha emitter" is worth looking at, although technologically difficult because of tight decay times.

Movement towards this goal (I think) : clinicaltrials.gov/ct2/show...

Something abut Actinium, as an alpha emitter. (ie not radium 223)

ncbi.nlm.nih.gov/pmc/articl...

[whatsinaname in reply to cesanon]

Xtandi is not that impressive, is it, according to Dr. Myers ??

My quack has recommended Xtandi after docetaxel. Before Zytiga.

The reason ?? The quack said that Zytiga has to be taken with prednisone

whereas Ztandi does not. I am diabetic. He also said that Xtandi is far more powerful

than Zytiga and he would therefore prefer to treat my aggressive PC with Xtandi.

[cesanon in reply to whatsinaname]

I don't recollect the details of Myers then current opinions, but they were fairly nuanced. Not black and white for and against decisions.