Skip to main content

Search
Best of 2013

Cancer Immunotherapy: Early Gains

|

Rebecca Gardner_Best of_Cancer Immunotherapy

Seattle Children’s work to cure cancer using reprogrammed T cells transitioned from treating mice to helping people in 2013.

 

Jensen_Best of_Cancer Immunotherapy

The dream of curing cancer without chemotherapy and radiation took a leap forward in 2013, with promising results in Seattle Children’s first cancer immunotherapy clinical trial and the opening of a second trial for children and young adults who have relapsed acute lymphoblastic leukemia (ALL).

The first two patients in the Phase 1 trial (called PLAT-1 or Pediatric Leukemia Adoptive Therapy-1) responded positively to T-cell therapy, which involves drawing blood from the patient, reprogramming their own infection-fighting T cells and then infusing the blood back into the patient’s body to destroy the cancer cells. Both patients – a 23-year-old woman and a 19-year-old man – experienced complete remission of their ALL and then underwent successful stem cell transplants. Both continue to do well.

The pace of patients entering the trial is expected to pick up in 2014, thanks to changes in the trial parameters by the U.S. Food and Drug Administration (FDA). PLAT-1 was initially open to patients ages 18 to 26 who had relapsed ALL, were responding poorly to chemotherapy, and had not yet had a bone marrow transplant (BMT). It is now open to all ages and the waiting period between patients has been shortened.

“Cancer immunotherapy is in its very beginnings, but as more patients are treated here and around the country, there is better understanding of what to expect. As more is known, we get to move more quickly,” notes Dr. Michael Jensen, director of the Ben Towne Center for Childhood Cancer Research (BTCCCR) at Seattle Children’s Research Institute. Jensen joined Children’s in 2010 to translate his lab findings on reprogramming T cells into cures for patients.

Gardner_Best of_Cancer Immunotherapy

In December 2013, Seattle Children’s opened a second cancer immunotherapy trial (called PLAT-2) for patients whose ALL relapsed after BMT. There are few viable treatment options for children and young adults who have reached this point. Dr. Rebecca Gardner is the principal investigator for both trials. The cellular technology designed for PLAT-2 uses purified populations of T cells and an advanced version of the CD19-specific chimeric antigen receptor. This trial also introduces a suicide switch that can eliminate reprogrammed T cells in the body, if necessary.

“PLAT-2 is for patients who have failed BMT, and it is likely the last therapy they’ll get. If the patients in this trial don’t relapse after T-cell therapy, it sets the stage for asking whether cancer immunotherapy can replace bone marrow transplant,” says Jensen.

Solid tumors are next

Preparations are underway at BTCCCR to launch its first solid tumor clinical trial for relapsed neuroblastoma under the direction of Dr. Julie Park. “Leukemia is the ‘low-hanging fruit’ of cancer immunotherapy. Lymphocytes are easy to manipulate to die – they do it every time an infection ends,” notes Jensen. “Solid tumors create environments within the tumor that are hostile to the immune system.”

The team has begun engineering T cells that can overcome the tumor’s hostile microbe environment. It requires a more advanced level of T-cell engineering, including identifying the appropriate receptor on the tumor cells that the reprogrammed T cell can bind to, and designing a way to eliminate the reprogrammed T cells if necessary. “We’re at a transformative moment in medicine. Imagine what it must have been like to be a pediatrician after the polio vaccine was rolled out and all those wards crammed with kids on iron-lung machines simply emptied out,” says Jensen. “That’s the hope for kids in Seattle and all over the world battling childhood cancers.”

“If patients who already failed BMT don’t relapse after T-cell therapy, it sets the stage for asking whether cancer immunotherapy can replace bone marrow transplant.”
– Dr. Michael Jensen