James Adair, PhD, Professor of Materials Science and Engineering, Biomedical Engineering and Pharmacology, Biomedical Engineer at Penn State University, Chief Science Officer at Keystone Nano, discusses the research being done on using nanotechnology to potentially treat cancer patients.
Interview conducted by Ivanhoe Broadcast News in July 2017.
Ceramide Nalipizone; tell me a little bit about it, how did you get to the point where you were looking at this particular agent?
Adair: Our pharmacologist, Mark Custer, had been studying it. When Mark and I met each other the first week of January in 2004, he was considered one of the world’s experts in Ceramide. At the time, Ceramide was an experimental chemotherapeutic that had several unique properties. It only killed cancer cells, it did not cause death in non-cancer cells. Healthy cells stayed healthy, their metabolic cycle slowed down a little bit, but it did not result in the cell’s death. To someone like me, who’s a cancer survivor, that’s awesome.
I do want to go into that if you don’t mind. When were you diagnosed, were you in the middle of research?
Adair: I don’t mind talking about my life experience. Cancer is like Voldemort, we should say it out loud. Yes, ironically. I have to go back a bit, I had an enlarged heart at one point. It runs in the family; my father had it, one of my brothers had it. We’re very sensitive to this one cold virus, it’s like an allergic response, only it causes your heart to expand, and that’s a bad thing. I wound up getting lifted from Mount Netnate down to Hershey. I was in and out of a coma, but I had enough presence of mind to say, hey guys, can you fly over the stadium? And they did. It was Joe Paterno’s three-hundredth win that day against Bowling Green. It was cool; they even tilted the helicopter and left the door open because no one on the helicopter, including myself, thought that I was going to survive. I went through that, my family and I went through that, and I had a new perspective on the matter. I thought maybe I could rebuild my heart and one of the local cardiologists gave me a script to see a nutritionist, she didn’t even blink. She laid out a diet for me, and after two years my heart had normal function and size. I became quite close to my cardiologist at Hershey, Larry Sinoway, and he’s now a collaborator. I try to use all of my diseases for that purpose. Hershey is a great place. Anyway, when I got the green light that I recovered from something that should have killed me, I thought about looking into Nano science to have more impact. I felt like we were in a unique position to manipulate these particles that were only a little bit bigger than protein molecules. I began looking around that particular in 2003; I was attending a lot of meetings about the subject. I was at a meeting in Soul Korea when another colleague gave a nice talk about using colloidal, that means very small, silicon dioxide used as surface decoration to deliver drugs and imaging. I was thinking about how we’ve been making composite Nano particles, which mean we had small cores and metals and semiconductors with silicon dioxide or titanium dioxide coatings, and I thought that we could use that as a diagnostic agent. I had a wonderful graduate student, Sara Rouse, now Sara Rouse-Janisek, and I came back and said Sara, would you like to try and put some fluorescent molecules into silicon dioxide? And she goes, sure Dr. Adair. Four months later we had these beautiful colored Nano particle suspensions. I thought this could be used for the medical diagnostic that we wanted. I talked to our vice president for intellectual property here at Penn State at the time, and I said, who down at Hershey can I talk to. I know I was going to talk to Larry Sinoway and some of the other clinician scientists that I knew. But he didn’t even blink he said Mark Kester. In 2004, Sara and I drove down to Hershey the first week, made the rounds, met Mark, and within about two and a half minutes we decided to go forward with the calcium phosphate, not the silicone dioxide. Calcium phosphate occurs naturally in the human body, it metabolic processes for the body to manage it without any inflammatory response is all in place. The first thing Mark wanted me to work on, of course, was Ceramide. I became part of his Ceramide crew. Meanwhile, Mark had been working for probably fifteen years at that time on Ceramide and Nanoliposomes. He was quite passionate about the Ceramide Nanoliposome’s being transformative as a chemo therapeutic. The paradigm around chemo therapeutics is base, these were all developed in the late fifties and the early sixties, and they’ve continued to develop. But the paradigm more or less kills the cancer, and it tries not to kill the patient. But with Mark’s system, you can kill cancer without harming the patient, and that’s a big deal. We did some encapsulation work; we helped Mark characterize his Nanoliposome’s because we’re pretty good at measuring particles down to molecular sizes. In 2005, I started thinking that between the calcium phosphate and the Nanoliposome’s, we had something that would help people. I wasn’t willing to just hand it off to another company. I thought that wow, we could do something good. I knew Jeff Davidson by that point, so I talked to Mark first about Jeff, then we had a conversation with Jeff and the three odd buddies got together and formed Keystone Nano. That would have been around May 2005.
If you could describe for me how this works and what they would see?
Adair: In 2005, Sara Rouse defended her PhD during the development process. We found that we could encapsulate flora force, we encapsulate Ceramide, and she showed the initial efficacy for the Ceramide in the calcium phosphate. But I wanted to keep firm boundary conditions, because I felt that the regulatory process to get these into human beings was going to be difficult. It’s a nano particle, and it turns out that it is diagnostic and therapeutic. One of the first flora force that we encapsulated was edosian and gray. The FDA approved the two infrared optical agents in 1959. Methalane blue doesn’t give you the transparency that the edosian and gray does. We have to be able to see the flora force in the human body. We went with edosian and gray. We read our first animal trial to evaluate the diagnostic for human breast cancer, particularly egregious and triple negative human breast cancer. We used an animal model to place human cancer into the breast flaps of mice, so it came as close to mimicking human cancer in a living host. We did tail vein injections, and we didn’t quite know what we were going to see with the edosian and gray. We were among the first to encapsulate anything, so we did a number of points; fifteen minutes after tail vein injection, thirty minutes, etc. We kept looking at particles, and they kept showing up within four days which is very unusual. They were getting cleared benignly through the liver and the GI tract, but they were accumulating in the cancerous tumors that showed up as bright spots in the neuro-infrared imaging that we were doing. We didn’t know the outcome, but we kept the first set of animals in a cage for about a month. One of the post doc in charge of it, Brian Barth, was checking out the animals and he noticed that the tumors weren’t growing in some of the animals. But they were growing in one of the animals. There are four animals in these cages for the controls with the edosian gray calcium phosphate calicut nano particles. At thirty days, he took another infrared image, and we didn’t see the tumors. We didn’t see the edosian and gray, that was long gone and degraded. But we saw either very, very small tumors in one or two of the animals, and no tumors in another, and quite large tumors in another animal. However, this was intended to be a short term study, so we weren’t sure what animal was what. Mark, Brian and Erhan and I were involved in designing the formulations. Erhan was helping with the imaging with Brian, and we began dosing animals to give them additional, but prescribed, photon treatments. We wound up giving them about twelve points six milligrams per centimeter squared. This consists of about a three-minute exposure to the neuro-infrared light which you can’t see. Your cat can see the neuro-infrared but humans can’t. Sure enough, the controls did what cancer does, took off exponentially, enormous tumor growth and the calcium phosphate calicut with the ICJ flat-lined. That was a wow moment.
So what did that say to you?
Adair: The edosian gray, which has been used to look at the retinopathy in the eye and clearance in the heart and liver, has its therapeutic use. That was the wow moment. With the right combination, it cleared the material only in the particles. The free dye got removed very quickly out of these animals. But all of a sudden, we’re stopping the growth of highly aggressive triple negative human breast cancer tumors in its tracks. We looked at mouse cancer and mouse breast cancer in a mouse, that also stopped. So different animal model, different cancer. We looked at pancreatic cancer; we looked at osteosarcoma. I’m usually not the smartest person in the room; the real brilliance came from Castor and Mark when they looked at chronic myeloid leukemia, non-solid cancer. No one had ever used this photodynamic therapy on non-solid cancer. Where does the blood go? Non-solid cancer is cancer of the blood. They radiated the spleen of the animal, and we did a survival evaluation. With no optimization of the dosing regimen, almost thirty percent of the animals survived and probably cured. It was another wow moment. Here’s a non-solid tumor in the animals and we are exposing the animals to light and various concentrations of the edosian and gray, far below the equivalent human concentrations, and we’re getting this profound therapeutic effect. Mark Kester and Brian Barth began looking more detailed about this, and they found that it resurrects the immune system of these animals. And that was quite a revelation. There was something that a lot of the current research was doing and trying to do. This would have been in a paper that we wrote in 2011. We showed the effect of cancer on the immune system in these animals in 2013.
At what point where you diagnosed with cancer, were you in the middle of this research when this happened?
Adair: I was diagnosed with cancer, but I cared more about my wife. Bernie was diagnosed with breast cancer in September 2007. I was diagnosed in September 2008 with colon cancer. To be honest, it was much more soul sucking for me to be Bernie’s caregiver than it was for me to go through the treatment myself. I sat on my cancer. If we can’t make jokes about colon cancer, what cancer can you make jokes about? I do remember thinking as I went through my twelve rounds of chemo, damn, I wish we had the particle ready. But they weren’t, so I just stuck it out, hung on by my fingernails toward the end of the process. Bernie and I argue about how many operations she should have, but we’re both healthy and whole today. I also had a colonoscopy yesterday. Folks, get your colonoscopy at fifty or earlier. I was fifty-six because I was kind of stupid.
You waited?
Adair: Yes, I thought heart disease was going to kill me, to be honest.
Were both of you fighting cancer at the same time or was Bernie clear?
Dr. Adair: No, there were points in time when I was down at Hershey and she was out it Pittsburgh, and we were both getting treatment. Good times. We don’t like September at all.
When were you free of cancer and declared…
Adair: Well you never really, once your body has thrown this curve at you kind of in the back, I don’t you know, I’m in complete remission. I had my colonoscopy yesterday, I put it off until fifty six and I’ve lost track of how many colonoscopies I’ve had since. I was Stage 3 metastatic colon cancer. I had somewhat longer odds, but you know so far God hasn’t taken me, I’m still here.
I want to talk about where you are now in terms of the Ceramide?
Adair: Clinical trial. Mostly thanks to Mark, Jeff, and Melissa Peret, I’ve looked over people’s shoulder and jogged their elbows if I felt they needed it. But we’re in Phase 1 clinical trial with the Ceramide Nanoliposomes.
And what will the Phase 1 do?
Adair: It’s for maximum tolerated dose.
What do they anticipate will come from Phase 1, what do you hope will come from Phase 1, what will researchers find?
Adair: In the run up to the Phase 1 clinical trial Keystone Nano submitted a investigative new drug proposal to the FDA. What the FDA approved was called a maximum tolerated dose. Now part of the pre-clinical and what goes in to this proposal to the FDA were evaluations of maximum tolerated dose in two animal models. This would be mice and dogs. The maximum tolerated dose for the Ceramide was very large, much larger than almost all chemotherapeutics that are conventional chemotherapeutics, because they would be toxic to even healthy cells. The unique aspects of the Ceramide was shining through the investigative new drug. And so after maybe a year or two, it took about eleven years to get to this stage. But after a year or two of working on the submission, developing the scale up and having a good manufacturing facility do the manufacturing which is what you have to do. The company has to remove themselves from any kind of conflict of interest. Because of course we want to see people get helped with this so the FDA has strict guidelines in that regard. So we dotted the I’s and crossed the T’s, we learned an awful lot going through this process. And we’re ready hopefully to go on several additional formulations that are in the pipeline.
Is it given as an IV, or an oral?
Adair: No, IV. In my naiveté, when I first started working on this, I thought oral would be nice. But the trouble with oral, particularly with conventional therapeutics, is that it is highly unlikely to determine the specific amount of dose that gets into the bloodstream. Everyone resorbs drugs somewhat differently. They have to survive the relatively low PH of the stomach as well. We would have to coat them with enteric agents. It’s given by IV because you know the exact dosage and you have a pretty good of the volume of blood in a given patient.
What is your hope sitting here in 2017, what do you want to see in the next three years in terms of this
Adair: Hopefully, we change the paradigm about cancer. Kill cancer, do no harm to the patient.
How optimistic are you?
Adair: I was hoping it would only take a year. Not twelve years, but I’m very optimistic.
In your mind what is the potential impact on people?
Adair: Getting cancer treatment would be like getting a vaccination. That’s what I hope. That’s kind of in the video club, but it will be routine. I thought I was very cool when I got my diagnosis and Bernie, and I talked because I had a colonoscopy. They found a large polyp, but they took more than a week, and we knew that they were double checking, and I probably had cancer. I had to drive over to Geisinger in Danville to pick up my tissue and go down to Hershey where my colorectal surgeon is, and this was the day after I got the word. I got to Hershey, I went to check in a hotel, and I didn’t have my wallet with me. I wasn’t quite as cool as I thought I was.
How long was your treatment?
Adair: First I had surgery, they took out about twelve inches of large intestine. That was sort of like getting kicked by a mule in the middle of your stomach. I don’t know if a mule has ever kicked you, but I’ve been kicked by a horse, it’s not fun at all. They gave me about six weeks to recover from the surgery, and then I started my chemo November 4th, 2008, and I ended April 4th, 2009. Twelve rounds, every two weeks. It was like having bad flu and then some. But I also had no nerve; I couldn’t feel anything in my hands, and in my legs from upper thigh to about half way down.
Has that come back?
Adair: Most of it. It’s getting there; I’m very optimistic. I couldn’t taste or smell anything. I couldn’t even feel myself breathe in because everything was numb or gone. The feeling was gone. But I was a lot of fun at dinner because I had to watch my hand pick up the fork and I’d take the food, and I’d stick myself in the cheek. My boys laughed, and I encouraged them.
Again the colonoscopy you went in for diagnostic, were you having any symptoms?
Adair: No, no, no, I go in every three years now that’s the protocol. In the immediate aftermath, it was every year, for three or four years. Now it’s every three years. And that’s a good thing.
What compelled you to go in for that first one?
Adair: Larry Senoway, my cardiologist, beat me up pretty good. He has been beating me up for six years. But I figured I had survived heart disease; I’d better make sure I don’t have colon cancer. We never had colon cancer in our family. Although, my mom did die from pancreatic cancer. So we had been touched. My grandfather and godfather both died from systemic cancer in the sixties. But back then, the cancer was systemic.
Is there anyone that hasn’t been touched by cancer?
Adair: When I give talks, I usually ask the audience is there anyone in the room that hasn’t been touched in some way by cancer and rarely do I get a hand raised. I think cancer has touched everyone. It’s time to turn it from the Emperor of all maladies to something we get a vaccination for.
END OF INTERVIEW
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