"The immune system has evolved to police the body for infections and diseased cells, but it has a difficult time recognizing malignant cells since they largely appear normal to the immune system," said lead study author, Renier J. Brentjens, M.D., Ph.D., medical oncologist in the Leukemia Service at MSKCC.
"The idea is that we can take a patient's own T cells, re-educate them by inserting a gene into them that will enable them to produce a receptor to recognize B cell cancers, and then return them to the patient where they should be able to attack and kill the tumor cells."
Because the technique uses a patient's own T cells, there is little risk of compatibility issues or rejection, as there might be with human stem cell transplant, Dr. Brentjens
adds.Human stem cell transplant, following radiation or chemotherapy, is currently incorporated into the treatment of several B cell malignancies.
In order to get T cells to recognize B cells, Dr. Brentjens
colleagues created a gene that encodes for a cell-surface protein - an artificial T cell receptor called a chimeric antigen receptor -- designed to specifically bind to CD19, a molecule found on the surface of B cells and B cell cancers.Antigen receptors are what allow T cells, in combination with other parts of the immune system, to recognize and attack infected or malignant cells.This chimeric gene, formed from active portions of several immune system-related genes, creates the chimeric antigen receptor protein called 19-28z, which does not require other co-stimulatory signals to fully activate T cells, according to Dr. Brentjens
. Dr. Brentjens
colleagues used an engineered retrovirus to insert the chimeric antigen receptor gene into T cell DNA.
"The repeated boosts of new T cells during therapy to improve T cell persistence enhances the efficacy of these T cells in eradicating cancerous B cells," said Dr. Brentjens
."This concept of T cell persistence being critical to treatment efficacy is one we are further investigating in current and upcoming clinical trials."
The results have given the researchers further evidence that the technique will work in humans.When transplanted back into a patient, these engineered T cells could then attack and kill tumor cells bearing the CD19 protein."CD19 is not found on the surface of bone marrow stem cells, so these modified T cells are reasonably safe since they should not attack other blood forming cells in the bone marrow following treatment," Dr. Brentjens
Based on the results of their findings, the MSKCC
researchers are currently conducting a clinical trial using this method in patients with chemotherapy-resistant CLL.CLL is currently considered an incurable cancer, Dr. Brentjens
said, although the disease generally progresses slowly.