Boston Children’s Hospital has been quietly changing the future of health for every child, here and around the world, since 1869. Named the number one hospital for care in the country, we are also the largest research center for pediatric medicine anywhere. Each year the conference proceeds benefit a new research initiative at Boston Children’s Hospital, as well as unique collaborations between Boston Children’s and the Broad Institute. Since inception in 2012, the Boston Investment Conference has generated more than $20M to accelerate the most promising research aimed at better treatments for sick children in the near term.
2022 Boston Investment Conference Awardee
Teaching the immune system to target a dangerous childhood cancer
Roberto Chiarle, MD Researcher, Department of Pathology, Boston Children’s Hospital
Neuroblastoma is one of the deadliest childhood cancers, and its most virulent forms—those resistant to chemotherapy—account for 15% of all cancer deaths in children worldwide. But there is an exciting new development in the global effort to tackle this devastating illness. Boston Children’s researcher Roberto Chiarle, MD, is ready to bring new treatments for the disease to clinical trial.
Dr. Chiarle’s strategy is to re-engineer patients’ naturally occurring immune cells to target a specific protein—ALK—that’s both unique to such cancer cells and required for their survival. In pre-clinical models, Dr. Chiarle has already shown that these hyper-charged immune cells, known as ALK.CAR-T cells, can target and kill the hardest-to-treat forms of the disease, even when spread in multiple organs.
The answer lies in the anaplastic lymphoma kinase (ALK) oncogene, a cancer-promoting protein that helps neuroblastoma and similarly difficult cancers thrive. Other researchers have developed drugs to inhibit ALK activity, but these methods only delay cancer progression; they do not stop it completely, as cancer cells inevitably grow tolerant to them.
That is where Dr. Chiarle’s strategy differs. Instead of inhibiting ALK, Dr. Chiarle uses it as a molecular tag for destruction, ensuring that ALK-positive cancer cells are efficiently detected and destroyed by the patient’s own immune system. In addition, the combination of ALK inhibitors with ALK.CAR-T cells generates an extremely potent cocktail of therapies against the same target, a powerful dual hit that tumors cannot survive. The specificity of ALK.CAR-T therapy also promises that the new treatment will spare normal tissue. Moreover, because the ALK protein is also expressed by other types of cancers, Dr. Chiarle’s work could have far-reaching impact on a wide range of malignancies, including other solid tumors.
Support from the Boston Investment Conference will enable Dr. Chiarle to launch the crucial human trials needed to save lives and effectively combat neuroblastoma. This critical work will pave the way to new treatments and offer fresh hope for children with cancer and their families.
Roberto Chiarle, MD
Attending Hematopathologist, Department of Pathology
Boston Children’s Hospital