In a recent article that appeared in Science Magazine, Amy Boland described her twelve-year quest to find a cure for the cancer that invaded her lymph system.
At first, standard chemotherapy did shrink her tumors. But after about six years, the lymphoma tumors began to regrow.
In an effort to stop the cancer from progressing, Amy received a bone marrow transplant which in some cases has provided a cure.
However, it again only had a temporary effect, so Amy agreed to try other treatments. These included a type of drug known as immune checkpoint inhibitors. The therapy gave her some relief for a just short while.
A final effort involved chimeric antigen receptor or CAR-T therapy. Amy’s T cells were removed, engineered by her doctors to destroy the lymphoma, then infused back into her body.
T cells, known as “killer cells”, develop in the thymus gland. They have the ability to kill virus-infected cells.
CAR-T destroyed any evidence of cancer, but again only for two years.
About Designer Antibodies
Amy was still determined to get her lymphoma under control. In October 2018 she entered a clinical trial that was evaluating an entirely different way to train her immune system to destroy tumor cells.
The procedure involves using a bispecific antibody, called a molecular rope, to tether Amy’s T cells to her tumor cells. This would cause the immune system to go on the attack.
The drug (mosunetuzumab) was similar to CAR-T in that it was aggressive. Although Amy had to be hospitalized several times due to side effects, in a short while she was in remission. Amy, at age sixty, has continued to be free of cancer at the one-year mark after being taken off the drug. She is grateful to finally being able to live free of cancer and cancer treatments.
The trial in which Amy participated is ongoing. The American Society of Hematology gave an interim report on the bispecific antigen trial. It stated that 46 out of 124 non-Hodgkin lymphoma patients, who had unsuccessfully tried other therapies, saw their tumors shrink.
Bispecific Antibodies
Many complex diseases are caused by multiple factors. Standard drugs are generally developed to target only one foreign substance (antigen). Therefore, focusing on only one target may be ineffective. In fact, it is possible that cells may react to the suppression of a receptor by producing another receptor.
Bispecific antibodies are designed to treat complex diseases by using one molecule focused on two disease targets.
Natural antibodies (immunoglobulin) are a primary defense against infections with two target arms binding to one target antigen.
Bispecific antibodies are designed in a laboratory with two targeting arms binding to two different antigens at the same time. These antibodies can be mass-produced while CAR-T cells must be specifically produced for each patient.
Room for Improvement
The new bispecific drugs are not yet providing patients with the same long-term remissions that are sometimes seen with CAR-T cell therapy.
Also, two deaths were reported after patients were tested with the bispecific antibodies. The researchers suspect that the deaths were caused by immune responses due to the drugs.
The bispecific drugs share the same drawbacks as CAR-T therapy in that they have thus far proven to be less effective against solid tumors than against lymph and blood cancers.
The other similarities are the risk of liver damage or the cytokine “storms” that result from immune overreaction.
The immune system reacts in both treatments by sending out a substantial quantity of toxic cytokines (signals). The results can be fever or sometimes organ damage.
The good news is that research is moving quickly to remedy these side effects. One such improvement is a redesign of the bispecifics whereby a different type of immune cells (natural killers) are being targeted. This approach selects the cancer cells and reduces the risk of targeting healthy cells that may be carrying minute amounts of a cancer antigen.
According to a biochemist at Scripps Research, engineering of antibodies has become sophisticated and efficient. At this writing, over sixty bispecific cancer antibodies are in various stages of clinical trials.
Amy Boland is still enjoying her freedom from cancer. She hopes it will last but says optimistically that if not, there will be other more advanced treatments. She refuses to worry.
