What Is ROR1?

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Topics include: Treatments and Understanding

Researchers are learning more about ROR1, an oncogene discovered on chronic lymphocytic leukemia (CLL) B cells. At the 2014 American Society of Clinical Oncology (ASCO) meeting, patient advocate Dr. Brian Koffman met with Dr. Thomas Kipps, a investigator of several trials evaluating the use of ROR1, to learn more about this oncogene and its potential use in targeting CLL.

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Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Brian Koffman:

Dr. Brian Koffman here at ASCO 2014.  You want to just quickly introduce yourself?

Dr. Kipps:

Yes.  My name is Dr. Tom Kipps.  I'm at the Moores Cancer Center.  That's with the UC San Diego School of Medicine.

Brian Koffman:

So we were talking about or just about to talk about to talk about ROR1.  So tell us what ROR1 is and why you're excited about this.

Dr. Kipps:

Well, we're kind of excited because—well, ROR1 we kind of stumbled into.  We actually had a protocol…

Brian Koffman:

That's R-O-R-1.

Dr. Kipps:

…ROR1, yes.  What it relates to is a surface protein that we identified on the surface of leukemia cells, and we did this because we had actually engaged in therapy where we were trying to generate vaccines for patients. As you know, we engineered patients' leukemia cells to try and induce—have the patient make an immune response against the leukemia cells, and some patients were able to mount immune responses, and we were able to monitor this.

Some patients developed antibodies, which bound to their own leukemia cells, and they bound to the leukemia cells of other patients.  And so we wanted to find out what that protein was, obviously, and it turned out to be ROR1.  Now, some of those patients anecdotally did very well for some time after therapy without requiring additional therapy.  And so we wanted to figure out what that was all about, and we spent a lot of time trying to figure out how ROR1 was working.  We're still working on that.

But it does seem so serve as a survival signal and a growth signal for the leukemia cell, and it facilitates things such as migration.  And we think that we've identified the way it works in terms of how it interacts with other cells within the so-called micro environment.

And it's critical to think about, but some patients could make an auto-antibody against the protein and affect its biology of the cell.

And so I think that we've wanted to try and mimic that, so we tried to generate a series of different antibodies.  We generated close to 100, and we found one that actually could mimic that activity, and so we worked on that and tried to with help from the California Institute for Regenerative Medicine.  We were able to help engineer that and make it a humanized antibody and actually have it produced under what's called good laboratory practice and to complete pharmacology studies and toxicology studies.  So this has now been filed for application for investigational new drugs, and we hope to be in clinical trials this summer.

Brian Koffman:

So ROR1, what I'm hearing that's different about this is it's on the leukemia cells.  Now, the CD20 is on the leukemia cells, but it's also on all B cells, so—but is this the difference with ROR1, that it's only on the leukemia cell?

Dr. Kipps:

This is the key, actually CD20 is on all B cells, and so when you target CD20 you deplete B cells, and one of the problems you might have is further immune suppression, which you have to be careful about.  That's not to say that you shouldn't use CD20 antibodies because they are quite effective against leukemia.  But with ROR1, we don't find it expressed on normal lymphocytes, and fortunately our antibodies seem to be quite specific for this protein and do not react with other tissues as well.

Brian Koffman:

Now, I've heard that there may be ROR1 on the pancreas. Is that an issue?

Dr. Kipps:

Well, that was one report with an antibody that was developed through a different method, and like with any antibody, you can have the antibody binding in a specific way sometimes there could be maybe some nonspecific cross reactivity.  So we were fortunate to find that the antibody did not bind to the pancreas or other tissues.

Brian Koffman:

Any offsite binding or issues that you're concerned about or any…

Dr. Kipps:

Well, I think it's critical that we look for that, but we've looked at studies even in primates and didn't see the problems with the antibody administration, so we're hopeful that this will be a very specific target against the leukemia cell.

And the exciting thing is that it works through a different process than this antibody-dependent cytotoxicity.  It seems to work by targeting the leukemic cell and taking away this signal.  In a way, it's sort of like with the same activities that we're having with these small molecules, and it may be a way

of delivering a one-two punch, which could be quite effective, particularly since we are concerned about patients going on some of these targeted therapies and having to stay on therapy life-long because, you know, I—we were talking about this earlier.  My mother-in-law had CML, and she after a while did not appreciate taking a drug every day for the rest of her life for her leukemia and wanted it to be over or—just to be over with it.

Brian Koffman:

So I want to switch to the targeted therapies, but I just wanted to hear a little—so the ROR1, do you have a sense of when that trial—that's a trial that's not available quite yet, or what's the story?

Dr. Kipps:

We filed what's called an IND application, and the FDA reviewing this.  It's very important that we have all the proper committees look over the protocol, and they have.  And so we hope that we might be able to get approval to initiate trials this June.  And so it's possible that we might be able to initiate clinical trials this summer, 2014.

So this could be another weapon that we can use.  I think what we really need to do is we can't be complacent right now.  It's very exciting, all the developments in CLL, unquestionable, but we should really try to take steps to see if we can cure this thing outright.  I would like to get patients with CLL and get rid of it like you would get rid of a pneumonia if you had an infection.

I mean, can you imagine having a pneumonia and going to the doctor, he says, well, if you take this pill, you won't be coughing as much and you won't have fevers, but the pneumonia is still present.  I don't think that would be as acceptable as if you can get rid of the pneumonia and go on with your life free of the disease altogether.  So I think that's a very important goal we should keep in mind.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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Page last updated on April 29, 2015