Serial Killer T cells Go on
Rampage Against Leukemia
It never occurred to me that a serial killer could be a good thing. But when the killer is an immune system cell called a T cell, and it’s programmed to attack thousands of tumor cells at a time, it becomes a wonderful thing.
I’m referring to a new gene therapy that recently surfaced from a brand-new, bold approach to killing cancer. The good news is, it’s working. In fact, even the researchers behind this treatment admit to being blown away. This one is really exciting. .
How a Doctor Reversed Her Husband’s
If you’ve ever known anyone with Alzheimer’s disease, you know how heart-breaking it can be. Not only does it destroy a person’s mental abilities and dignity … but it wipes out the person’s very personality, leaving behind a mere shell of a human being. The body is there for you to see, but the person you know and love no longer exists.
That’s exactly what happened to my colleague Dr. Mary Newport and her husband Steve. As Mary describes it, “I was watching my husband of 36 years fade away.”
In Mary’s words, it was “Strange to have no short-term memory and yet the information was filed somewhere in his brain. I knew he was locked up in there somewhere, if only there was a key to open up the areas of his brain that he didn’t have access to.”
Little did Mary know that she would soon find that very key.
Sensational results from a single shot
It started with a highly unusual approach to cancer treatment. Researchers at the University of Pennsylvania’s Abramson Cancer Center and Perelmen School of Medicine thought it would be a good idea to treat cancer patients with genetically engineered versions of the patients’ own T cells.
The pilot study started with a group of only three patients. Each patient had advanced chronic lymphocytic leukemia (CLL), and was essentially out of treatment options.
The protocol was to remove some T cells from each patient and then modify those same cells in the Penn vaccine production facility. Once removed, those T cells were reprogrammed to attack tumor cells.
After being reprogrammed, the modified T cells were infused back into each patient’s body.
Three weeks after the infusion, all three patients tested in the study experienced a dramatic response to the treatment. Two of them went into complete remission. The third experienced at least a 70% reduction in cancerous cells.
The researchers were blown away with the results. Lead researcher Carl June, MD, even enthused, “It worked much better than we thought it would.”
He went on to describe a 1000-fold increase in the number of modified T cells in each patient. “Drugs don’t do that,” said June. He also said each infused T cell led to the killing of thousands of tumor cells, destroying at least two pounds of tumor in each patient.
Treatment exceeds ‘wildest expectations’
The T cell “reprogramming” was done with something called a lentivirus vector, which encodes an antibody-like protein (called a chimeric antigen receptor, or CAR), on the surface of the T cells. CAR is also designed to bind to a protein called CD19, which is important because it differentiates the good cells from the cancerous cells.
Once a T cell successfully expresses the CAR protein, it hunts down and kills other cells that express CD19. This includes CLL tumor cells along with normal B cells. All the other cells in a patient get ignored — important, because this means few side-effects.
That’s impressive science right there. But even better than that, the research team also inserted a “signaling molecule” into the part of the CAR that exists inside the T cell. After binding to a CD19 protein and initiating cell death for the cancer, this signaling molecule tells the cell to make cytokines. In turn, these cytokines prompt other T cells to multiply. This generates new, good-guy T cells until all the cancer cells are destroyed.
Before this, the only real treatment option was a bone marrow transplant that has a 50 to 80 percent long-term success rate. As you can see from that statistic, this type of leukemia is fairly mild and treatable, even without this new T cell breakthrough. What’s more exciting is that the T cell therapy may be applicable to other cancers.
It’s interesting to note modified T cells have been used in previous trials, but with uninspiring results. The researchers involved in this trial describe the process as a “reawakening” of T cells that were suppressed by the leukemia. They also hope the treatment will stimulate something called “memory” T cells to provide protection against a relapse.
It’s that self-perpetuating aspect of this treatment that is truly amazing. Unlike chemotherapy, which has to be given again and again (often to the detriment of the patient receiving it), this treatment will persist over time, dividing and killing tumors.
Bright future for gene transfer therapy
The researchers involved say this work essentially provides a roadmap for attacking tumors of other types of cancers, including lung cancer, ovarian cancer, myeloma, and melanoma. They’ll start by moving forward with similar tests on other types of CD19-positive tumors, including non-Hodgkin’s lymphoma and acute lymphocytic leukemia.
In addition, they’ve already come up with a CAR vector that binds to mesothelin, which is a protein found on the surface of ovarian, pancreatic, and mesothelioma cancer cells.
The findings of this study were published in the New England Journal of Medicine and Science Translational Medicine. It’s big news on the cancer front because this is the first time researchers have successfully used gene transfer therapy to bring about an attack on cancerous tumors — and it’s all thanks to this idea of “serial killer” T cells.
The research that almost didn’t happen
The reason this treatment almost didn’t happen was a lack of funding. The National Cancer Institute and multiple pharmaceutical companies all declined to pay for the research. Their reasons are unknown, but a good guess is probably that the concept was too innovative. Interesting, because if you think about it, this approach works with the body’s natural defenses instead of dredging up yet another power-drug.
In the end, and thank goodness, philanthropic support came through. This included funds from the Alliance for Cancer Gene Therapy and the Leukemia & Lymphoma Society.
At some point, there will probably be a handoff to a pharmaceutical company, especially as larger trials get underway. Maybe some government funds will become available. In a better world, this discovery would be taken to market without Big Pharma’s help, but that’s probably too much to hope for. It will be interesting to see how much this costs when it finally reaches the public.
The other thing that tempers my enthusiasm a little bit is that the 5-year survival rate is reportedly 76 percent for CLL (chronic lymphocytic leukemia, the type that was treated in this study.) If that’s true, then conventional medicine was already having a fair degree of success with this disease, and the new breakthrough may be less than it seems. For all types of leukemia, the 5-year survival rate is claimed to be over 50 percent.
Let’s hope this new discovery improves those rates even more. And — most important in my view — let’s hope it works for other types of cancer.
We’ve been told by some alternative cancer doctors that they actually refer leukemia patients to conventional treatment centers because the chances of success are fairly good. Leukemia seems to be one of the rare types of cancer where conventional treatment is worth a go, especially if the patient has chronic leukemia, the mildest form of the disease.
In the meantime, this T cell treatment is one of the first major cancer breakthroughs that wasn’t supported by a pharmaceutical company, that shows excellent results, and works WITH the immune system instead of destroying it.
As we wait for the wheels of Big Medicine to slowly grind away on this thing, there are great natural remedies available right now. Our last issue reported on one of the most exciting. If you missed it, scroll down and take a look now.