Beating sarcoma – minus the side effects
Treatment attacks soft-tissue cancer tumors, spares healthy cells
When Chris Miller visited his doctor in 2011 with a swollen and painful leg, little did he realize the seriousness of his symptoms.
Miller’s left calf felt deeply bruised, but two separate ultrasounds disclosed nothing. With his pain worsening, Miller sought another opinion. This time, the doctor biopsied tissue from his leg. The diagnosis: myxoid liposarcoma, a rare soft-tissue cancer with a high risk of recurrence after treatment.
Standard treatment followed Miller’s diagnosis – six weeks of daily radiation to shrink the tumor, then surgery to remove it. When the cancer returned in 2013, a colleague at Kia Motors Manufacturing in Georgia, where Miller is vice president, recommended MD Anderson Cancer Center.
Miller and his wife flew to Houston, and at MD Anderson, they met Neeta Somaiah, M.D., associate professor of Sarcoma Medical Oncology.
Boosting the immune system
Somaiah is conducting clinical trials with a sarcoma vaccine that contains a tumor-specific antigen – a protein that is found only on cancer cells and not on normal cells. This antigen can stimulate the body’s immune system to attack the antigen directly, which in turn kills the cancer cells to which the antigen is attached.
In the case of sarcoma, an antigen named NY-ESO-1 seems particularly well suited for a vaccine. In patients with myxoid liposarcoma, over 90% express, or make, NY-ESO-1, compared to only about 10% with lung cancer.
“Because the rate of expression of NY-ESO-1 is so high, it’s a great option for sarcoma,” Somaiah says. “The neat thing about this antigen is that it’s not expressed on the surface of your normal cells. It becomes a great immune target. You can attack it, and you won’t have side effects to your heart or any other place in your body because you don’t have that antigen presented anywhere else.”
The initial clinical trial, in which Miller participated, tested LV305, an engineered harmless virus that is injected into the skin of patients with locally advanced, returning or metastatic cancer. LV305 promotes production of the NY-ESO-1 protein, which, in turn, stimulates the immune system to send cancer killing T-cells to destroy the NY-ESO-1-positive cancer cells. The treatment was injected every three weeks for four doses.
After treatment, Miller has had no recurrence of his cancer.
“I’ve gone from quarterly examinations at MD Anderson to semiannual evaluations. I have no limping, and I walk four to five miles per day with my responsibilities at the Kia plant,” he says.
Safe and well-tolerated
The next phase of the trial focused on Somaiah’s cancer vaccine candidate, named CMB305. In this trial, patients received LV305 – which worked so well for Miller, followed by G305, which functions as an immune response booster.
Results indicated that both treatments – the LV305 alone and the LV305 plus G305 – were safe and well- tolerated. Fewer than half the patients had side effects – fatigue, injection-site reaction or muscle pain – and those were low-grade reactions.
“I did not have anybody who had trouble tolerating it,” Somaiah says. “Patients from out of town were just flying in to get their vaccine and flying out. They, in fact, felt much better because they were coming off chemotherapy and all those side effects.”
Both treatments induced the desired immune response.
Reducing lag time
Research continues for the best combination of approaches to kill the tumor and keep it away.
“The potential downside of a vaccine is that it takes a couple of vaccinations before we can get your body to generate enough T-cells,” Somaiah says. “There’s a time lag before getting an effective therapeutic response.”
A new clinical trial is testing a way to reduce the time lag by starting with a large infusion of T-cells generated outside the body, followed by the vaccine to prolong the persistence of T-cells and the level of immunity.
“So far, we’ve shown that the vaccine works, generates an immune response and stabilizes tumors,” Somaiah says. “Hopefully these studies will lead to FDA approval and make this vaccine a treatment option in the very near future.”