V alpha-invariant NKT cells as a novel platform for cancer immunotherapy
Background
Neuroblastoma (NB) is the most common extracranial malignancy of childhood. About 60% of children with high-risk disease are not cured by current therapy and therefore require new treatment strategies. NKTs are a unique subset of white blood cells with antitumor properties. Our group recently showed that NKTs localize to the tumor site in NB patients and attack non-malignant cells called tumor-associated macrophages, which provide critical support for the survival and growth of the tumor cells. For the greatest effect of immunotherapy, NKTs must survive in the hostile environment at the tumor site and attack not only tumor-supportive cells, but cancer cells as well.
"I’d been trained as a pediatric oncologist in Moscow, Russia more than 20 years ago and primarily took care of children with high-risk or recurrent neuroblastoma. Since almost none of my patients survived (some of them dying literally in my hands, their faces and words still vivid in my memory), I realized that the available therapy was ineffective and that the situation could only be changed via research." -Leonid Metelitsa
Project Goals
Our published and preliminary results suggest that upon genetic engineering with a receptor for a survival factor called IL-7 and with a neuroblast-targeting molecule called CAR.GD2, NKTs will survive at the tumor site and have antitumor efficacy via targeting of neuroblast-supportive cells and neuroblasts themselves. In order to prove this, we will use NKTs from NB patients and employ established in our labs methods to genetically modify them with IL-7 receptor and CAR.GD2 constructs. Functional activity of these modified NKTs will be tested using in vitro and in vivo experimental systems. The best construct will be selected for subsequent phase I clinical trial of gene-modified NKTs in NB patients.
