HIV, the virus that causes AIDS, with the dangerous parts removed, is perfectly designed to invade a cell and allow genetic engineers to reprogram it.
There will be many breakthroughs coming using this technique. At the moment it looks like there is a successful treatment for Leukemia, even late stage, and possible other type of cancers too.
There is a new tool that can tell in 2 seconds whether a surgeon is cutting cancer or normal cells during surgery
Latest news from Italy, US and London where the Gene therapy technique is being practiced successfully
There is a new tool that can tell in 2 seconds whether a surgeon is cutting cancer or normal cells during surgery
Latest news from Italy, US and London where the Gene therapy technique is being practiced successfully
Carl H. June, MD
Director, Translational Research Program; Richard W. Vague Professor in Immunotherapy, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
Medscape: Adoptive immunotherapy, as I understand it, uses a patient's own genetically engineered T cells to treat leukemia in children and adults. Could you describe how the process works?
Dr. June: The protocol involves removing a patient's T cells and reprogramming them to attack tumor cells by genetically modifying them *
Medscape: What are the results to date of studies of the gene-transfer technology?
Dr. June: We have 3 phase 1 clinical trials that are ongoing: 2 at the University of Pennsylvania in adults with leukemia and 1 at Children's Hospital of Philadelphia (CHOP) in children with leukemia. We are planning to extend these studies to other centers.
The first 2 studies include 12 adults with chronic lymphocytic leukemia (CLL), and thus far, 9 of the 12 have had good responses to the gene transfer treatment. We have just concluded the initial study, and the first patient we ever treated, in July 2010, remains in remission. Actually, 2 of the first 3 patients we treated remain in remission, demonstrating that the results are durable.
In the children's study, led by Dr. Stephan Grupp at CHOP, 4 of the first 5 children we have treated have had complete remissions.
Medscape: What are the characteristics of the patients who have received the treatment?
Dr. June: We were required by the FDA to initiate the treatment in adults; children were not treated until a year later. In both adults and children, the patients were "end of the line" with advanced leukemia and with no other proven therapeutic options that were available.
Our hope is that if the treatment is effective in patients with late-stage disease, we will be successful, eventually, using it upfront as first-line therapy. Perhaps we could arrive at a point where leukemia can be treated without chemotherapy. Gene transfer therapy with engineered T cells may be an alternative to allogeneic BMT, when BMT is the only resort at present. [BMT - bone marrow transplant]
However, there is still a subset of patients who have been transplanted and then relapse after allogeneic stem cell transplants, and because there is no proven treatment option in this setting, the technique may be useful in those patients as well.
One of the children with pre B-acute lymphoblastic leukemia (ALL) in the phase 1 trial that I alluded to had relapsed after allogeneic BMT, and the CAR T cells induced a complete remission.
Medscape: What challenges remain in this treatment?
Dr. June: Dosage: Just as we would with other treatments, we need more experience. We don't know the optimal dose of T cells yet. This is more difficult to calculate than for drugs that are metabolized, because the genetically engineered T cells proliferate once they are re-infused into the patient. At the moment, it appears that we have to give a certain threshold number of T cells to the patient. A trial has just begun at the University of Pennsylvania, led by Dr. David Porter, who has been studying this approach in adults to identify the optimal dose.
We also don't know whether 1 treatment is enough to achieve remission. It may be that maintenance therapy is needed. We don't know yet whether the patients in remission will ever need another treatment. The answers to these questions related to delivery of treatment may be different in children vs adults.
[In my opinion these are minor challenges to a successful treatment]
Medscape: What is needed for FDA approval? [this is always the major challenge]
Dr. June: There is no precedent for FDA approval, so we can only speculate. This would be the first cell-based gene transfer therapy for cancer, representing new ground at FDA. Thus, our main challenge is probably how to go about obtaining FDA approval.
... Novartis made a major commitment, and now other biotechnology companies have expressed interest in investing in the technology as well.
I am optimistic that the recent industry investment will lead to the eventual widespread availability of the treatment on a broader scale. Our initial results have held up. Excellent results in the first 3 treated patients could have been a chance finding or a statistical fluke, but now we have treated 12 adults and 5 children and have continued to observe a potent activity of the treatment. Perhaps the most important finding is that the responses are durable.
Medscape: Do you envision using the genetically engineered T-cell treatment in cancers other than leukemia?
Dr. June: Early-stage pilot trials are being conducted in other cancers at the University of Pennsylvania, Memorial Sloan-Kettering Cancer Center, MD Anderson Cancer Center, Baylor College of Medicine, and the Fred Hutchinson Cancer Center. Animal models suggest that the treatment works in other cancers,[6] but we are in the very early days of learning whether it holds promise for non-B-cell blood cancers and other cancers in humans.
If you know someone that has Leukemia, and potentially other cancers, get them to a clinical trial at one of the centers mentioned above.
You can find other clinical trials here:
My father died from late stage renal cancer for which there was no cure and no treatment at the time he was diagnosed.
Had he been enrolled in a clinical trial, he might have been saved, as the particular trial, which I only found out about 3 weeks before his death, had a 40% success rate.
More technical details of the treatment.
*using an HIV-based lentivirus vector. The vector encodes an antibody-like protein fused to a cytosolic signaling domain, called a chimeric antigen receptor (CAR), which is expressed on the surface of the T cells and designed to bind to the CD19 protein.
When the T cells express the CD19 CAR, they kill cells in the patient's body that express CD19, which includes leukemia cells as well as normal B cells. The modified T cells do not interact with cells that do not express CD19, potentially limiting side effects caused by standard therapies. In addition, the binding of T cells to CD19 initiates the production of cytokines that trigger other T cells to multiply, creating a progressively larger army of T cells to destroy all the target cells in the tumor. Thus, in addition to an extensive capacity for self-replication, the CAR T cells could be called "serial killers."
