A new treatment has seen multiple patients achieve complete remission from some extremely aggressive forms of cancer—after being treated with a type of genetically altered HIV.
Researchers have been trying for decades to figure out how to use gene therapy to train a person’s own immune system to kill cancer cells; now, via a bioengineered form of HIV-1, scientists may have found a way. In clinical trials so far, out of twelve patients treated, nine experienced a drastic reduction in cancerous cells; five of those are presently in remission, free of cancer.
Viruses have frequently been used as carriers of altered DNA to reprogram other cells, because such alterations are exactly what they do naturally. To achieve the effect with patients’ T cells, Dr. Carl June, leading a research team in the Abramson Cancer Center at the University of Pennsylvania, employed HIV cells as more than just a model.
The virus that causes AIDS is a natural for such treatment, given the drastic effects it has on T cells. Dr. June admitted that the idea may sound frightening, but while the team is the first to use modified HIV cells for gene therapy to fight cancer, it has been used previously against other diseases, such as Epstein-Barr virus.
Patients who underwent the treatment did not become HIV-positive, as the virus used was disabled via genetic altering. It was subjected to DNA added from cows, mice, and humans, as well as from one virus that infects cows and another that infects woodchucks, leading to Dr. June calling it “truly a zoo.”
The clinical trial focused on B cell cancers such as acute lymphoblastic leukemia (ALL), the most common type of childhood cancer, and chronic lymphocytic leukemia (CLL), most often found in adults. B cells are a type of cell found in the immune system; T cells are supposed to identify and attack threats to the system, but when B cells become cancerous, the T cells fail to respond.
In the currently experimental treatments, a cancer patient’s T cells are collected, then genetically altered to recognize and bind to CD19, a protein found only on B cells; the clinical name for cells that have been altered this way is chimeric antigen receptor T cells, or CTL019 cells.
When injected back into the patient, they are able to target and kill B cells. Healthy cells are eliminated as well, but B cells are not required for the immune system to function; those with CTL019 cells simply require regular treatment with immunoglobulin infusions, which can be accomplished in the home. The CTL019 cells remain in the body for months or years, ready to replicate and attack again, thereby keeping the patient from experiencing a relapse.
Predictably, the treatment is not without risks; in the first pediatric patient to undergo the procedure, Emily Whitehead, the destruction of her leukemia cells also provoked an adverse immune response so severe she had to be admitted to the intensive care unit. Genetically altered T cells have also gone after healthy tissue in some previous cases, such as a woman with an advanced case of colon cancer who died after the T-cells apparently found a targeted protein also present in her lungs and attacked.
However, it should be noted that all the patients treated so far were considered to be terminal; chemotherapy and in some cases bone marrow transplants had failed, and many were too close to death to undergo further traditional treatment. Though chemotherapy is successful in most cases of B cell cancer—for example, 85% of patients achieve remission with chemo alone from acute lymphoblastic leukemia, a further 15% don’t respond to current treatments.
In addition, a course of chemotherapy also typically takes one to two years, and the effects can be devastating to both a patient’s physical and emotional health. Emily, at age 7, had already been fighting ALL for almost two years when she suffered a second relapse, while still undergoing chemotherapy for her first relapse. In contrast, despite her initially adverse reaction to the CTL019, just three weeks after she was treated tests revealed no signs of cancer. Over a year later, rechecks of her bone marrow still show her in complete remission.
Dr. June told Science Daily, “We’re hopeful that our efforts to treat patients with these personalized cellular therapies will reduce or even replace the need for bone marrow transplants, which carry a high mortality risk and require long hospitalizations. In the long run, if the treatment is effective in these late-stage patients, we would like to explore using it up front, and perhaps arrive at a point where leukemia can be treated without chemotherapy.”
It’s too soon to call CTL019 treatment a cure; the first experimental treatments were in 2011, and doctors don’t consider patients officially cancer-free until they pass the five-year mark without a relapse. There’s also no way to know how long the CTL019 cells last in the body, or how long they remain effective against cancer, but doctors are hopeful.
Fire With Fire:
Another video about Emily can be found here.
Patients aged 1 to 21 with B cell cancers such as ALL who are interested in CTL019 treatment may contact the Children’s Hospital of Philadelphia’s Cancer Center or call 267-426-0762.
Patients aged 22 or older may visit the Abramson Cancer Center to learn more about this study and to get further information.
Other open clinical trials at the Children’s Hospital of Philadelphia can be found via the Clinical Trials Search Tool.