Cellular immunotherapies involve the transfer of disease-fighting immune cells into a patient. Adoptive T-cell therapies employ a type of white blood cell — T cells — to eliminate cancer. The cells used for therapy can be T cells that already recognize the patient’s cancer and have been isolated from their blood or tumor. Or they can be T cells from the patient that are genetically engineered to target cancer.
Through our pioneering work on bone marrow transplantation we made the first definitive and reproducible demonstration of T cells’ ability to kill cancer cells. Since then, Fred Hutch scientists have been on the cutting edge of T-cell therapies for cancers, contributing numerous “firsts” in their development. Our research on T-cell therapies continues to push boundaries, making these strategies more effective and safer for more patients.
Genetically modified T cells come in two major types, based on the type of cancer-targeting receptor that is engineered into them. One type employs T-cell receptors, or TCRs, which are the molecular weapons natural T cells use to fight disease. The other type uses a type of synthetic receptor called chimeric antigen receptors, or CARs. The word “chimeric” refers to the fact that the receptors are built from parts derived from antibodies and other natural molecules.
Each type of engineered T cell has its own advantages. To date, the most promising results have been from CAR T-cell therapies in patients with certain blood cancers. But scientists are developing T-cell therapies for a wide range of malignancies, including blood cancers and a variety of solid tumors.
Fred Hutch scientists Drs. Phil Greenberg, Stan Riddell and teammates performed the first human study in the world of genetically engineered, target-specific T cells. Today, our multidisciplinary team of immunotherapy researchers continue to develop genetically modified T-cell therapies in the lab and clinic. Hutch scientists are mapping out the biological factors that cause these therapies to succeed or fail or what might cause side effects. They are using this knowledge to develop next-generation T-cell therapies that could help more people with more types of cancers, including solid tumors like breast and ovarian cancers.
Antibody-based treatments use highly selective immune proteins called antibodies. Hutch science led to some of the first approved antibody-based therapies for cancer, including Rituximab, the first so-called “magic bullet” drug for cancer. Building on the latest discoveries about cancer biology, our researchers are developing novel cancer-targeting drugs based on antibodies.
There are several varieties of cancer therapies that employ antibodies and cause tumor cell death through different means. In one type of antibody-based therapy, the antibody ferries a toxin or radioactive particle straight to cancer cells, sparing healthy cells and minimizing harmful side effects. Hutch researchers are pioneers in this area of antibody-guided radiation therapy. Research here led to some of the first approved radioimmunotherapies and our scientists continue to innovate and improve this targeted approach to cancer treatment.
In other antibody-based therapies, antibodies trigger tumor death by binding to cancer cells. Bispecific antibodies are designed to grab hold of a cancer cell on one end and an immune cell on the other, bringing them together so that the immune cell to attack. Perhaps the best-known antibody-based cancer therapies are checkpoint inhibitors, which help remove the brakes, or checkpoints, that restrain immune cells from attacking cancer cells. Hutch researchers are learning more about how best to use existing antibody-based drugs to maximize their effects against cancer.