Based on their research, showing that an exciting new form of cancer immunotherapy has activity in patients with glioblastoma, the most common and most deadly form of brain cancer, researchers from Massachusetts General Hospital (MGH) have created a new method that can make the immune therapy more effective for brain tumors and expands its application against other types of solid tumors. Their study is published in the journal Nature Biotechnology.
The treatment, known as T-cell therapy chimeric antigen receptor (CAR T), comprises collecting and genetic modification of patient-fighting immune T-cells to recognize specific targets (antigens) on the surface of tumors, and then return them to the patient . Two drugs CAR T cells have been approved by FDA for the treatment of non-Hodgkin's lymphoma, and acute lymphoblastic leukemia, respectively, cancer of the lymphatic system and blood.
But solid tumors such as glioblastoma, notoriously difficult to treat with conventional cancer drugs, because most drugs have molecules that are too large to cross the blood-brain barrier, and immunotherapy has its problems in this area, explains principal investigator Marcela V Mouse, MD Sciences, director of cellular immunotherapy in cancer MGH center.
"Previously, we did CAR T cells for glioblastoma, and one of the problems of glioblastoma is that not all cancer cells express purpose for which may be followed by a T-cell", - says Mouse, who is also an assistant professor of medicine at Harvard.
The purpose to which they sought, embodiment III is epidermal growth factor receptor (EGFRvIII), mutated protein causes a cancer that is present on the surface of many, but not all glioblastomas.
Therefore, to increase the effectiveness of CAR T cells, they decided to aim for a second antigen, natural or "wild type» EGFR. But because EGFR is present in many cells of the body, drugs targeting protein can cause serious side effects. To overcome this problem of toxicity, Mouse and his colleagues created the CAR T cell, which can be delivered into the spinal fluid at the base of the brain. When he gets to the brain, CAR T allocates the second type of immunotherapy, called bi- . specific T-cell angazherom or «BiTE» BiTEs - are antibodies that direct cell killing T cells to a particular purpose, are somewhat similar to the homing mechanism in a so-called "smart bomb."
Despite the fact that they are smaller than the drugs based on antibodies, BITES is still too large to cross the blood-brain barrier, if given intravenously, therefore the design CAR T, secreting BiTE, which they have created, can provide local tumor effects by targeting a second antigen, and it is a way to overcome this heterogeneity of the tumor. However, since it is formed on the other side of the blood brain barrier, and in small quantities, it does not cause toxicity to other organs.
When they are verified that human glioblastoma models, they found that a modified BiTE-secreting CAR Ts removes about 80% of the tumors.
This method promises to treat other solid tumors, says lead author Brian D. Choi, MD, of the department of neurosurgery at MGH.
Scientists argue that the biggest obstacle in their efforts to undertake in the field of clinical trials is to provide financial support for research on humans.