IIRC Research

Next-Generation Immunotherapy Research    

Immunotherapy is a broad term for a family of treatment approaches designed to empower the human immune system to overcome cancer and other diseases.

The immune system can locate, recognize and attack invaders like the cold virus. However, the immune system is not always able to eliminate cancer. Scientists at Fred Hutch are discovering new ways to tap into the immune system's inherent disease-fighting power and give it the upper hand against cancer. Hutch scientists are studying fundamental immune mechanisms with an aim toward translating new approaches for patients to the clinic. These include adoptive T-cell therapies and antibody-based therapies.
 

Next-Generation Therapies

Adoptive Cellular Therapies   

T-Cell Therapies 

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 Engineered T-Cell Therapies  

CARS and TCRs

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. 

Tumor-Infiltrating Lymphocyte (TIL) Therapy

TIL therapy is an example of a cellular therapy based on cancer-recognizing T cells already in a patient’s body. The T cells used in experimental TIL therapies have responded to a patient’s cancer, but they have not been able to gain the upper hand. Scientists isolate these T cells from tumor samples that were removed in surgery. 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.  

Left: Dr. Aude Chapuis examines a patient at the Bezos Family Immunotherapy Clinic. Right: Dr. Seth Pollack is working to develop new ways to enhance sarcoma patients immune systems.

Robert Hood

Radiolabeled Antibody-based Therapies    

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, 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.

Other Immunotherapies

Cancer immunotherapies take many forms beyond antibodies and T cells, including vaccines that prevent or treat tumors.

At Fred Hutch, Dr. Martin “Mac” Cheever leads the Cancer Immunotherapy Trials Network, through which top academic immunologists design and conduct trials of different types of high-priority, promising cancer immunotherapy agents. These agents include checkpoint inhibitors, which are proteins designed to block the braking mechanism that cancer cells use to shut down the immune response.

The IIRC facilitates inter-institutional collaboration to advance the most cutting-edge ideas in the field. For example, Hutch scientists are collaborating with University of Washington researcher Dr. Nora Disis to test experimental vaccines to prevent breast cancer.

Matthias Stephan
Dr. Matthias Stephan continues developing injectable nanoparticle reagents, including ones that can rapidly program T cells to attack tumors. Ongoing research is focused on targeting melanoma, prostate, ovarian and pancreatic cancers. Robert Hood / Fred Hutch

Translational Research

Immunotherapy is revolutionizing cancer treatment. Yet the approach is not successful for all cancer patients. IIRC researchers hope to bring the power of immunotherapy to more patients by answering lingering questions in the field, including why some patients’ tumors fail to respond and why some relapse after initial successful treatment. We are probing deeper into the fundamental interactions between the immune system and tumor to address these questions. Our areas of study include:

  • A deeper understanding of how the immune system functions, which may shed light on how it can be better deployed against cancer
  • The tumor microenvironment: all the cells, structures and molecular factors surrounding the tumor, and how they affect its progression and response to treatment
  • The cells and signals that shape whether a T cell can become part of an effective, long-lived cancer-fighting army
  • Immune cells beyond T cells, and their role in shaping an anti-cancer immune response
  • Next-generation technologies, including synthetic biology and nanotechnology, as the basis for new immunotherapeutic approaches