IIRC Research

T-Cell Therapies 

‘Adoptive’ cellular immunotherapies involve the transfer of disease-fighting immune cells into a patient, generally employing white blood cells known as T cells. For example, T cells that already recognized a patient’s cancer have been isolated from their blood or tumor, expanded and reintroduced as therapy. Increasingly, T cells are collected from the patient or a donor and are genetically engineered to target a patient’s disease.

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 against 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.

Tumor-Infiltrating Lymphocyte (TIL) Therapy

TIL therapy employs cancer-recognizing T cells already in a patient’s body, including T cells that have responded to a patient’s cancer, but have not been able to gain the upper hand. Scientists isolate these T cells from tumor samples that were recovered from the patient. Then, they can manipulate the cells in the lab – including growing large numbers of them – and reinfuse them into the patient.

Our scientists are also developing methods to precisely measure and characterize TILs in a patient’s tumor to provide more accurate prognoses and help predict whether certain immunotherapies are likely to help that patient.

CARS and TCRs

Genetically-modified T cells come in two major types, based on the type of disease-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 Fred Hutch scientists are developing T-cell therapies against 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 that 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, as well as to improve outcomes after organ transplantation.

Antibody-based cancer therapies

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/Rituxan®, the first so-called “magic bullet” drug for cancer patients. 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 can 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.