Immunotherapy. A very sexy word, indeed. It's the hot topic in cancer treatment these days, and in fact my last post featured an update on some of the most recent and terrifically exciting progress being made in this area, using CAR-T technology. But while retraining or reeducating or literally rebranding our T-cells and immune systems to fight cancer is one concept, using something that previously maimed and killed, in part by avoiding our immune systems, is quite another!
Such is the case for a newly exploding area of medical research, which is the treatment of glioblastoma using the oncolytic virus approach - in this case using the feared polio virus - as reported on by the "60 Minutes" current affairs program on CBS last night. Scott Pelley and his team followed a groundbreaking new clinical trial for two years to bring us the story. In a truly ironic state of affairs, scientists are now beginning to successfully use pathogens that have previously had the capacity to kill us, to instead kill cancer cells inside us. Now that's what I call progress!
"One of the scientists told me that it takes a killer to kill a killer...."
Although that seems like a fairly drastic take on the situation, we must remember that when our T-cells are doing what they are supposed to be doing, they also kill abnormal cells or those expressing epitopes of "non-self". So, modifying a virus such that it invades and attacks cancer cells, specifically, whilst leaving normal cells unharmed, seems to be a genius take on the problem - in principle - as long as it doesn't kill people in the process.
Thus it was very heartwarming to hear that the FDA has granted this approach "breakthrough status" due to results obtained to date in clinical studies ongoing at the Preston Robert Tisch Brain Tumor Center of Duke University in the United States. This means that hundreds of glioblastoma patients will gain access to this audacious therapy ahead of approval by the FDA, due to it's new "fast track" status. In some cases at least, this offers patients with essentially no hope of survival, a chance at not only survival but of being cancer-free.
Somehow, seeing patients afflicted with this deadly brain malignancy being injected with a dose of a pathogen that mankind wants globally eradicated by 2016, was both fascinating and rather fearful at the same time. Anytime scientists, clinicians or patients step into the dark unknown, there is always palpable excitement and anticipation laced with a healthy dose of foreboding - because you don't know until you try it - and the waiting can be excruciating.
It goes without saying that the bravest individuals of them all are those who volunteer for such trials, when they already have been put through so much, often via surgery, radiation and chemotherapy. But the demand is growing, and the Tisch screens some 1,000 glioblastoma patients each year vying for a spot on the trial, and as word spreads that number is likely to increase. When you've quite literally got nothing to lose, you will try anything.
The fascinating outcome of this early Phase I trial is that the dream result was obtained in selected cases; one doesn't expect to see a major impact on disease in such a trial, but given that it is being conducted in cancer patients who have exhausted their options, it's always a possibility. So it is with a few individuals who manifested remarkable responses to treatment with this modified polio virus.
One striking example was 20-year-old Stephanie Lipscomb who had been diagnosed with a brain tumor the size of a tennis ball, which was surgically resected followed by "as much radiation as you can have in a lifetime" as well as chemotherapy. That was in 2011, but by 2012 the cancer was back, and her only remaining option was that which had never been tried. The scary thing (but ultimately saving grace) in her response, was that shockingly and disappointingly, two months after her treatment began the tumor actually looked bigger. It wasn't working; or so doctors thought.
The neuro-oncologist who was leading the charge wanted to terminate the treatment and put Stephanie back on traditional treatment, but the young woman refused. Rather remarkably, after four or five months and with the help of MRI analysis, the team realised that her tumour only looked bigger - but it's increased circumference was actually inflammation, only around the site of the tumour - and that was due to her reawakened immune system!
This took everyone by surprise but was a lightbulb moment in that, effectively, it appeared that infection with the modified polio virus had broken down external defences of the tumour, exposing it from its protective shield, thereby allowing the young woman's (healthy) immune system to begin infiltrating and breaking down her tumour. And? Some 21 months of continued shrinkage ensued, until the cancer was gone - today she is in full remission and is cancer-free - which is a spectacular result by any standards!
Naturally, not everyone achieved similar success, but so far for the 40-odd patients who have been in the program, they have on average extended their lives by 50%, and three patients remain cancer-free, three years later. It was amazing to see the ventricles reopen and folds in the brain reappear as the tumour shrank in 70-year-old retired cardiologist Fritz Anderson, who four years later considers himself cured and travels with his wife around the world.
There have been crushing disappointments also, including those where classical Phase I parameters were being tested, and doctors learnt that increasing the dose (by as much as three times over what worked in the first few patients who are alive) does increase the inflammatory response, but by too much. Such was the case for Donna Clegg, who battled the inflammation bravely for many months but ultimately lost that battle and passed away about a year ago.
She, like all the patients in the polio trial, was a "medical explorer" as Scott Pelley quipped, but I like to think of them as medical heroes as well, for how much new and vital information they have provided to modern medicine in the fight against cancer. One such unexpected piece of information was the striking observation that patients previously exposed to the polio virus treatment have greatly improved responses to chemotherapy, subsequently. That opened up the eyes of the physicians, and will be an added weapon in their arsenal moving forward.
Speaking of physicians, I would be remiss without mentioning the dedicated researchers and clinicians involved in this polio trial. They are molecular biologist Dr. Matthias Gromeier and neuro-oncologists Drs. Henry Friedman and Annick Desjardins, collectively led by Dr. Darell Bigner who directs the Tisch. I daresay that to the patients in the polio trial, as well as their families and friends, as well as more than a few of us, these individuals also merit the term "medical heroes". Let's hope that the upcoming expanded clinical study will shine an even brighter light on everyone concerned!
Although that seems like a fairly drastic take on the situation, we must remember that when our T-cells are doing what they are supposed to be doing, they also kill abnormal cells or those expressing epitopes of "non-self". So, modifying a virus such that it invades and attacks cancer cells, specifically, whilst leaving normal cells unharmed, seems to be a genius take on the problem - in principle - as long as it doesn't kill people in the process.
Thus it was very heartwarming to hear that the FDA has granted this approach "breakthrough status" due to results obtained to date in clinical studies ongoing at the Preston Robert Tisch Brain Tumor Center of Duke University in the United States. This means that hundreds of glioblastoma patients will gain access to this audacious therapy ahead of approval by the FDA, due to it's new "fast track" status. In some cases at least, this offers patients with essentially no hope of survival, a chance at not only survival but of being cancer-free.
Somehow, seeing patients afflicted with this deadly brain malignancy being injected with a dose of a pathogen that mankind wants globally eradicated by 2016, was both fascinating and rather fearful at the same time. Anytime scientists, clinicians or patients step into the dark unknown, there is always palpable excitement and anticipation laced with a healthy dose of foreboding - because you don't know until you try it - and the waiting can be excruciating.
It goes without saying that the bravest individuals of them all are those who volunteer for such trials, when they already have been put through so much, often via surgery, radiation and chemotherapy. But the demand is growing, and the Tisch screens some 1,000 glioblastoma patients each year vying for a spot on the trial, and as word spreads that number is likely to increase. When you've quite literally got nothing to lose, you will try anything.
The fascinating outcome of this early Phase I trial is that the dream result was obtained in selected cases; one doesn't expect to see a major impact on disease in such a trial, but given that it is being conducted in cancer patients who have exhausted their options, it's always a possibility. So it is with a few individuals who manifested remarkable responses to treatment with this modified polio virus.
One striking example was 20-year-old Stephanie Lipscomb who had been diagnosed with a brain tumor the size of a tennis ball, which was surgically resected followed by "as much radiation as you can have in a lifetime" as well as chemotherapy. That was in 2011, but by 2012 the cancer was back, and her only remaining option was that which had never been tried. The scary thing (but ultimately saving grace) in her response, was that shockingly and disappointingly, two months after her treatment began the tumor actually looked bigger. It wasn't working; or so doctors thought.
The neuro-oncologist who was leading the charge wanted to terminate the treatment and put Stephanie back on traditional treatment, but the young woman refused. Rather remarkably, after four or five months and with the help of MRI analysis, the team realised that her tumour only looked bigger - but it's increased circumference was actually inflammation, only around the site of the tumour - and that was due to her reawakened immune system!
This took everyone by surprise but was a lightbulb moment in that, effectively, it appeared that infection with the modified polio virus had broken down external defences of the tumour, exposing it from its protective shield, thereby allowing the young woman's (healthy) immune system to begin infiltrating and breaking down her tumour. And? Some 21 months of continued shrinkage ensued, until the cancer was gone - today she is in full remission and is cancer-free - which is a spectacular result by any standards!
Naturally, not everyone achieved similar success, but so far for the 40-odd patients who have been in the program, they have on average extended their lives by 50%, and three patients remain cancer-free, three years later. It was amazing to see the ventricles reopen and folds in the brain reappear as the tumour shrank in 70-year-old retired cardiologist Fritz Anderson, who four years later considers himself cured and travels with his wife around the world.
There have been crushing disappointments also, including those where classical Phase I parameters were being tested, and doctors learnt that increasing the dose (by as much as three times over what worked in the first few patients who are alive) does increase the inflammatory response, but by too much. Such was the case for Donna Clegg, who battled the inflammation bravely for many months but ultimately lost that battle and passed away about a year ago.
She, like all the patients in the polio trial, was a "medical explorer" as Scott Pelley quipped, but I like to think of them as medical heroes as well, for how much new and vital information they have provided to modern medicine in the fight against cancer. One such unexpected piece of information was the striking observation that patients previously exposed to the polio virus treatment have greatly improved responses to chemotherapy, subsequently. That opened up the eyes of the physicians, and will be an added weapon in their arsenal moving forward.
Speaking of physicians, I would be remiss without mentioning the dedicated researchers and clinicians involved in this polio trial. They are molecular biologist Dr. Matthias Gromeier and neuro-oncologists Drs. Henry Friedman and Annick Desjardins, collectively led by Dr. Darell Bigner who directs the Tisch. I daresay that to the patients in the polio trial, as well as their families and friends, as well as more than a few of us, these individuals also merit the term "medical heroes". Let's hope that the upcoming expanded clinical study will shine an even brighter light on everyone concerned!
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