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Replies to post #363991 on NorthWest Biotherapeutics Inc (NWBO)
forumreader35 Thursday, 04/11/19 09:21:53 AM
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Select Novel Approaches to Glioblastoma—Part 2
Published in Oncology and Expert Opinion / Interview · April 10, 2019
Interview with
Steven Brem MD
Interview by
Aman Shah MD
https://www.practiceupdate.com/content/select-novel-approaches-to-glioblastoma-part-2/76518
Dr. Shah: So, we spoke earlier in part one of this program about some of the new research that you’re doing with DNA vaccines and conjugates with Pseudomonas toxin. Could you tell us some other interesting research you’re doing on novel therapies in neuro-oncology?
Dr. Brem: Yes. We just completed a study with Tocagen, which is a viral therapy, which will also stimulate the immune response and also uses a novel form of chemotherapy where it takes an antifungal drug that is converted genetically to an oncolytic drug. So it’s a very clever approach, and that’s a large multi-center study and that’s being analyzed right now. And we learned at this meeting that their plans to roll out a new trial through the NRG for newly diagnosed using viral therapy and we’ve heard of the poliovirus, we’ve heard of the many viral studies coming from multiple centers in Boston, Houston, and so on, and about viral therapy. And whatever the virus is, they all are oncolytic. They kill the new glioma cell, liberate new antigens, or neoantigens, which are then recognized by antigen presenting cells.
We’ve also been very active in the DCVax, which was started at UCLA but now extended to Penn and other sites. And the interesting thing of that trial, which we reported some preliminary data, is that a large percentage of the patients are now living beyond 3 years, so that is a unique approach in that the patients own tumor creates their very individual vaccine looking at their own panel of antigens. So we’re excited by that approach and we’ll be hearing more about that in the future.
Dr. Shah: Okay, so my understanding of the DCVax is that you have to take the tissue out and then generate something against the dendritic cells within that admixture.
Dr. Brem: Yes.
Dr. Shah: Could you tell us a little bit more about where that therapy stands as of now and what kind of efficacy we're getting?
Dr. Brem: Well, a very large multi-national study was concluded and so that is going to…as the data matures, that will be going to FDA. We hope that that gets approved. We don’t know, but it’s an exciting study.
Dr. Shah: Okay, so talking about getting tumor cells out and generating something against it. It seems that you are also either working on or are involved with CAR T cells in glioblastomas, so please walk us through how that works.
Dr. Brem: Well, that is an exciting effort. It’s being led at the Abramson Cancer Center by Donald O’Rourke and his team, Zed Binder. I’m involved in that group, and it has just been funded by the Abramson Cancer Center as a translational center of excellence, so there’s a huge effort underway with neurosurgery and the Parker Institute, Abramson Cancer Center, Carl June’s Laboratory, many other laboratories trying to develop the next generation of CAR T cell. So we are…we just published a first-in-man phase I human trial that showed biological activity. And now because we’re dealing with a tough foe, the glioblastoma, we’re working on potentiating this by taking down some of the tumor defenses, looking at checkpoint inhibitors, combining it, supercharging the CAR T cell vaccine in a combination therapy, so that will be the next generation. That’s the future.
Dr. Shah: So, my understanding is that perhaps part of the reason why PD-1s have not been as promising in glioblastomas is glioblastomas somehow seem to not be very rich in T cells when you sample them, so there’s something stopping them.
Dr. Brem: There’s stromal barrier and there are inhibitors like TGF-ß, IL-6, the TNF-a, there’s cytokines. Also, we’ve been very interested in looking at macrophage polarization. And I’m part of a group that published this year in Nature Communications led by Yi Fan, who presented at this meeting, showing that if you block IL-6, you could redirect the macrophage from a tumor-suppressing state, the M2 state, to the M1 immunostimulatory state, so we hope to partner with pharma on that and develop the clinical trials based on that discovery.
Dr. Shah: That is fascinating, and of course, the CAR T cell strategy makes perfect sense because you create them in vitro and then put them in.
Dr. Brem: Yeah, so ultimately, we feel by attacking the tumor microenvironment as well as creating a vaccine directed to the antigens on the tumor, we’re going to have really a new class of therapy.
