Researchers are learning to teach a person’s own immune system to fight the cancer battle. It’s the science of immune-oncology (I/O), and Dana-Farber Cancer Research Institute made the breakthrough discoveries in this science nearly two decades ago. Dozens of bioscience companies are now conducting their own research in developing I/O therapeutics.
Why are immune-oncology therapies so important?
The big advantage of I/O therapy is the adaptability of its cancer-fighting mechanism. The individual’s cancer will mutate over time – and utilizing I/O therapies, the patient’s immune system can also evolve to attack this target, explains Dr. Mark McKenna, a practicing physician, entrepreneur and visionary who monitors medical trends.
In the early 2000s, Dana-Farber scientists discovered that many cancer cells carry checkpoint proteins called PD-L1 and PD2 that ward off an immune system attack on tumors. Significant research has been devoted to developing and testing drugs that block those proteins.
These insights serve as the foundation for research today into I/O therapies that will trigger an immune response tailored to a specific patient’s tumor. These therapies must be dynamic and able to evolve to match the evolving T-cells. This work produced drug agents capable of blocking proteins, sending cancers into long-term remissions.
Impressive survival reports
The field of I/O has accrued impressive survival reports during the past five years, and multiple bioscience companies are targeting various mechanisms geared toward “braking” the immune system by reversing T-cell suppression. Efficacy has been limited to a subset of patients with a subset of cancers. Researchers have also witnessed modest benefits in major tumor types like melanoma and lung cancer.
Dana-Farber’s success has revolutionized the treatment of metastatic melanoma, one of the most difficult cancers to treat. More than 2,000 patients have been treated with the drug ipilimumab since then, and about 20 percent have benefited – with the vast majority still alive today.
Researchers continue to work on better understanding the drug and the disease, and extending the drug’s benefits to more patients. New studies suggest that patients with a poor response to the drug may benefit from a combination of checkpoint inhibitors. A trial is underway of this combination in patients with advanced melanoma, reports Dr. Mark McKenna.
Dana-Farber’s latest victories
These successes have led to an early-phase trial of a drug that blocks another checkpoint protein – PD-1 – on T cells. The early results show that nivolumab can drive metastatic melanoma into remission or hold it in check for more than two years in some patients. The benefits occur quickly and persist in some cases after drug use has discontinued, says Dr. Mark McKenna.
In a study of patients taking both ipilimumab and nivolumab, more than 61 percent had their tumors shrink, compared to 11 percent who received ipilimumab alone. The combination eradicated all visible signs of the cancer – a complete response – in some patients. However, because the combination therapy had harsh side effects, more study is needed. Dana-Farber researchers are committed to studying the approach in treating other cancer types.
Small bioscience startups join the movement
Dana-Farber’s work is the cornerstone of research from Juno Therapeutics, Surface Oncology, and dozens more bioscience companies. Juno Therapeutics is one bioscience company bent on cracking the chemical codes that govern human T-cells and cancer cells, says Dr. Mark McKenna.
Juno is researching the use of human T cells as therapeutics to drive one of the next important phases in medicine, with cell-based cancer immunotherapies utilizing the chimeric antigen receptor (CAR) and high-affinity T cell receptor (TCR) technologies to genetically engineer T cells to recognize and kill cancer cells.
Juno has shown compelling evidence of tumor shrinkage in clinical trials using multiple cell-based product candidates to address refractory B-cell lymphomas and leukemias,
Longer term, Juno aims to develop their cell-based platform to address a broad range of cancers and human diseases. While this science is still in its early stages, the clinical results have been inspiring and gaining FDA “fast-track” designation to speed the R&D process, states Dr. Mark McKenna.
Juno’s researchers believe they have not yet peaked in I/O discoveries, and view their position as the “front edge of a wave of new therapies and immune-directed targets, and their combinations, that offer real promise to broaden, deepen, and extend the longevity of immunotherapy benefit.” They intend to target other immune components beyond T-cells – believing that these non-T-cell directed approaches are on the cusp of validation in cancer therapy, reports Dr. Mark McKenna.
Surface Oncology is another bio-startup that has focused on these non-T-cell mechanisms. Both clinical and animal studies have exhibited potential for this approach, especially when combined with T-cell directed agents. It’s an exciting frontier with promising results, potentially giving cancer patients greater options beyond surgery, radiation therapy, and chemotherapy – which, as we all know, can be debilitating.
About Dr. Mark McKenna:
Mark McKenna, MD, MBA is a Medical Doctor licensed in Surgery and Medicine by the Georgia and Florida State Board of Medical Examiners. He is a passionate patient advocate. Dr. McKenna served as National Medical Director of Life Time Fitness Inc. until July 2016. In July 2017 Dr. McKenna became the CEO/Founder of OVME a consumer facing, technology enabled, medical aesthetic company that is reinventing elective healthcare. Dr. Mark McKenna currently lives in the Atlanta area with his wife and young daughter. He is a voracious reader.