Doctors and scientists at St. Jude Children’s Research Hospital are working with colleagues across the world to develop new ways to kill tough-to-treat cancers using children’s own immune cells that have been reprogrammed. A recent collaboration with colleagues in Shanghai Children’s Medical Center has found a new immunotherapy combination that resulted in remission for virtually all children – 99 percent – who had relapsed B-cell acute lymphoblastic leukemia (ALL). Of the 225 patients in the study, nearly three-quarters also didn’t experience another relapse in the 12 months following treatment.
The findings were published in November 2022 in the Journal of Clinical Oncology. The research is part of a broader $12.9 billion strategic plan by the research hospital to accelerate progress toward cures and means of prevention for childhood catastrophic diseases, while improving access to quality care for children with catastrophic diseases everywhere.
This most recent science builds on work St. Jude began 60 years ago, when doctors on the Memphis campus combined chemotherapies to treat ALL in children. That pioneering approach helped substantially raise survival rates at St. Jude for children with ALL, which have grown from less than 5 percent when the hospital started to about 95 percent today. This study used a similar combination treatment approach to address the toughest cases of relapsed B-ALL.
“We have learned that you must hit the cancer cells with combination therapies with different mechanisms of action at the same time to cure patients,” said Ching-Hon Pui, MD, chair of the St. Jude Department of Oncology, who called the 99 percent remission “an excellent rate.”
The research was made possible because of relationships built over decades among scientists and physicians from St. Jude and multiple Chinese institutions.
“This research is evidence of what we can accomplish together and is just the latest example of scientific discoveries our teams can achieve,” said Carlos Rodriguez-Galindo, MD, chair of the St. Jude Department of Global Pediatric Medicine. “The results of this study will bring hope and options for cure to children with refractory leukemia all over the world.”
The study used two types of immune cells re-engineered in labs called “chimeric antigen receptor (CAR) T cells.” The CAR T cells work like the body’s natural immune cells but are engineered to target specific proteins found on certain cancer cells. Cancer cells often dodge killing by the immune system, allowing them to survive and grow.
Pui said this study mixed two types of CAR T cells together.
“Our thought was if one type of CAR T cells cannot kill all the cancer cells, the other type of Car T cells may kill those cancer cells that remain,” he said.
This study also benefited from advances in CAR T cell preparation which used to take over a month. This time, scientists were able to create the necessary CAR T cells in one week.
“Because our CAR T-cell preparation can be done quickly, the patients received the treatment in good clinical condition,” said Pui. “For other approaches, you need to give the patient additional chemotherapy to prevent the progression of the disease and try to keep the patient in good shape for 35 to 40 days to prepare the CAR T cells. The patient may become too sick or have too many leukemia cells before they receive CAR-T cell treatment. This faster approach offers a big advantage.”
Physicians involved in the study were also interested in using CAR T cells as an alternative to radiation for treating patients with extramedullary relapse (EMR), which is when the cancer returns outside of the bone marrow. The common practice is to use radiation to treat EMR. But radiation is linked to complications in the years after treatment such as the development of a secondary brain tumor, neurocognitive problems and restricted growth among patients treated for central nervous system relapse, or sterility among those treated for testicular relapse.
“While this novel combined immunotherapy approach will not work in all patients with EMR,” Pui said, “you can spare a substantial proportion of them from damaging therapy. Physicians should give patients a trial of CAR T cells before radiating them.”