(BPT) - When the Cancer Research Institute (CRI) was founded in 1953, little was known about cancer and even less about the immune system. CRI was the first - and for many decades the only - research funding organization that believed that we could one day harness the immune system as a powerful weapon against cancer. Since then, the field of cancer immunology has blossomed and immunotherapy has revolutionized how cancer is treated, thanks in part to work funded by CRI.
This year marks CRI's 65th anniversary. As part of the celebration, the nonprofit dedicated to cancer immunotherapy research released a list of 30 of the most important CRI-funded scientific breakthroughs. Each milestone can be traced directly back to CRI, which has supported more than 3,200 scientists and doctors at top institutions around the world.
Though distinct, each of these breakthroughs provided crucial pieces to the complex puzzle that CRI has long sought to solve: how the immune system can be used to save the lives of those with cancer.
Many CRI-funded foundational discoveries helped establish immunotherapy as a viable treatment approach for cancer. One particularly important discovery occurred in 1976, when a team led by Lloyd J. Old, M.D., CRI's founding scientific and medical director, revealed the existence of spontaneously occurring anti-tumor immune responses in cancer patients.
Many of today's advancements in cancer treatment are a direct of result of these foundational breakthroughs, made possible in part by the $384 million in donor support that CRI has invested in scientists over the last six decades.
Checkpoint inhibitors that target the PD-1/PD-L-1 pathway have been approved for eleven major cancer types in the United States and around the world, thanks in part to early work funded by CRI. While working in the Emory University lab of Rafi Ahmed, Ph.D., CRI-funded fellows E. John Wherry, Ph.D., and David Masopust, Ph.D., laid the groundwork for these therapies by showing that targeting this pathway could restore the activity of "exhausted" T cells.
These treatments, however, weren't the first checkpoint immunotherapies approved by the FDA. The first, which targets CTLA-4, was approved in 2011 after a breakthrough in a phase III clinical trial with advanced melanoma patients. CRI-funded postdoctoral fellow Dr. Frank Borriello was part of Dr. Arlene Sharpe's team at Harvard Medical School that was one of the first to help clarify the role of CTLA4 in immune responses, while James P. Allison, Ph.D., 2018 Nobel Prize recipient, current director of CRI's Scientific Advisory Council, and chair of the Department of Immunology and the executive director of the Immunotherapy Platform at the University of Texas MD Anderson Cancer Center, is regarded as a pioneer and one of the driving forces behind the clinical development of anti-CTLA-4 immunotherapy.
Expanding immunotherapy's applications
Beyond checkpoint inhibitors, immunotherapies like vaccines can educate patients' immune systems about what cancer "looks like," while others incorporate patients' immune cells directly. These cell-based immunotherapies continue to show great promise and are improving survival for many patients, including children, living with cancer.
In 2002, Dr. Cassian Yee, a CRI-funded clinical grantee at the Fred Hutchinson Cancer Research Center in Seattle (now at MD Anderson Cancer Center), helped lead groundbreaking work that was among the first to show that cancer patients' immune cells could be removed, enhanced in the lab, and then used to help fight their tumors. This work launched the development of many adoptive T cell immunotherapy approaches - including chimeric antigen receptor (CAR) T cell therapy, an approach recently approved by the FDA for the treatment of some types of leukemia and lymphoma.
Bacteria and viruses
People often associate bacteria and viruses with the infections that can arise from these organisms. However, because of their ability to stimulate the immune system, bacteria and viruses can also promote immune responses against cancer. In fact, the first use of immunotherapy in the 1890s - by CRI's "grandfather" Dr. William B. Coley - involved infecting cancer patients with bacteria to help stimulate their bodies to attack the cancer.
Since then, we've learned much more about the roles these microorganisms play in the context of cancer immunotherapy. In 2015, CRI postdoctoral fellow Dr. Leticia Corrales, while working in the lab of the University of Chicago's Dr. Thomas F. Gajewski - a member of CRI's Scientific Advisory Council - discovered that mice with "good" bacteria were better protected against tumor development and responded much better to checkpoint immunotherapy. Subsequent work by Dr. Gajewski showed that this same connection exists in human cancer patients too, spurring a number of bacteria-based prognostic and therapeutic approaches being evaluated right now.
Looking to the future
Over the past 65 years, CRI has focused on cancer research with one goal in mind: to unleash the immune system's power to cure all cancers.
"Many people living with cancer today have been able to live longer, healthier lives thanks to the power of immunotherapy and we're now seeing decades of research come to fruition," said Dr. Jill O'Donnell-Tormey, chief executive officer and director of scientific affairs at the Cancer Research Institute. "We're thrilled to have been a major part of the progress made to date, but more research needs to be done and that's why those of us at the Cancer Research Institute will continue to fund the best, most promising scientists in cancer immunotherapy research until all cancer patients benefit from these treatments."