May 29, 2020 by John Fernandez
Defeating Cancer: Immunotherapy Advances on Promising Path
Over the last few years, immunotherapy has evolved into a very promising new frontier for fighting some types of cancers, sometimes reprogramming a person’s own immune system into attacking and destroying tumor cells.
Many of these breakthrough treatments are still in the clinical trial phase. But their progress so far has been striking, fueling optimism that chemotherapy and radiation, and their often crippling side effects, may soon — maybe a decade from now — no longer be the primary method of destroying cancer cells.
“Ten years from now, immunotherapy will be an integrated part of some cancer treatments,” said Guenther Koehne, M.D. Ph.D., chief of Blood & Marrow Transplantation and Hematologic Oncology at Miami Cancer Institute. “In some cases, these immunotherapies will cure patients without any chemotherapy necessary. This approach will continue to evolve. And there will be other diseases treated with immunotherapy only and will be treated successfully.”
Proof of the power of immunotherapy came in 2018 when researchers at the National Cancer Institute (NCI) revealed how a 52-year-old Florida woman achieved complete regression of her metastatic breast cancer which had been unresponsive to all other treatments. Her cancer had spread to her liver and other parts of the body. More than four years after her treatment, the patient, Judy Perkins, is still cancer-free. The case of Ms. Perkins is concerned a landmark in the advancement of immunotherapy.
Previously, immunotherapy drugs had shown little effectiveness against the kinds of solid tumors that represent about 90 percent of cancer deaths, including those of the breast, prostate and colon. This new approach, which was used in Ms. Perkins case, was featured in the journal Nature Medicine and was hailed by cancer researchers as a development that will open a new frontier in cancer immunotherapy for solid tumors.
How T-Cells Target Tumors
Although the treatment, which is complex and time-consuming, is far from becoming available to most cancer patients, it holds much promise, experts say. A team headed by Steven Rosenberg, M.D., chief of the Surgery Branch at National Cancer Institute’s Center for Cancer Research, sequenced the DNA of one of Ms. Perkins tumors to find which mutations were unique to her cancer. This treatment relies on immune system cells known as tumor-infiltrating lymphocytes, or TILs.
These TILs are often found in tumors, and they are potential markers that reveal a person’s immune response against the tumor. The ones used on Ms. Perkins were picked because they could target four mutant proteins that were present in all of her cancer cells. An exhaustive search of her blood and a sample of her tumor turned up only 11 of these immune cells, so the scientists spent four months growing billions of copies in the lab.
“These new tumor-specific antigens are different in every single patient, but once you have them identified they are very specifically targeted by TILs,” explains Dr. Koehne. “And if you can target them with these T cells, they recognize those cancer cells without inducing any side effects because they don’t recognize any normal cells.”
Ms. Perkins, who had metastatic breast cancer, came to the trial after receiving multiple treatments, including several chemotherapy and hormonal treatments that had not stopped her cancer from progressing. “I have definitely hit the jackpot,” Ms. Perkins, a retired engineer from Port St. Lucie, told the Los Angeles Times.
“We’ve developed a high-throughput method to identify mutations present in a cancer that are recognized by the immune system,” Dr. Rosenberg said in a statement released by the National Cancer Institute, which is part of the U.S. government’s National Institutes of Health. “This research is experimental right now. But because this new approach to immunotherapy is dependent on mutations, not on cancer type, it is in a sense a blueprint we can use for the treatment of many types of cancer.”
Immunotherapies for Blood Cancers
Cancers of the blood generally do not form solid tumors, such as those in Ms. Perkins case. But immunotherapies to fight so-called blood cancers have been evolving at a faster clip.
Last year, the U.S. Food and Drug Administration (FDA) approved two different types of immunotherapies — ones that target two common types of blood cancers, including lymphoma (cancer of the lymphatic system) and leukemia (a cancer of the white blood cells.)
Both approved gene therapies treat blood cancers that affect the production and function of a person’s blood cells in certain individuals who have exhausted other treatment options. Most of these cancers start in the bone marrow where blood is produced. In most blood cancers, the normal blood cell development is disrupted by uncontrolled growth of an abnormal type of blood cell.
The first FDA approval came in August of last year when the U.S. agency gave the go-ahead to Kymriah for certain pediatric and young adult patients with a form of acute lymphoblastic leukemia (ALL). The FDA called it an historic action that ushers in a “new frontier in medical innovation.” The FDA’s second approved immunotherapy came in October when it greenlighted a treatment called Yescarta, which is aimed at adults with a certain type of blood cancer called “diffuse large B-cell” lymphoma. It is also the first gene therapy for certain types of non-Hodgkin lymphoma (NHL).
Each dose of Yescarta represents a customized treatment for each patient. It is also referred to as “chimeric antigen receptor T-cell therapy,” or CAR-T therapy. The patient’s T-cells, a type of white blood cell, are collected and genetically modified to include a new marker that targets and kills the lymphoma cells. Once the cells are modified, they are infused back into the patient.
“After all these years now, the immunotherapies for hematological malignancies and solid cancers are basically in full swing and that will not go away,” says Dr. Koehne. “They will develop further after these initial promising results seen in patients with both solid tumors and also with CAR-T cells in hematological malignancies such as acute lymphoblastic leukemia (ALL) and Non-Hodgkin’s disease. There has been significant progress. And these will be established as an existing treatment opportunity for patients.”