As a member of the cancer research community who has dedicated her professional career to studying and fighting cancer, I am starkly aware of the devastating impact of this disease as it continues to be the second leading cause of death globally. At the same time, I am incredibly encouraged by the work being done to transform cancer care through ongoing research and innovation in oncology.
Throughout my career, I have been driven by a personal commitment to the relentless search for new ideas that drive this innovation. Perhaps most notably is the use of next-generation technologies to help discover novel therapeutic agents with the potential to change the lives of, and restore hope for, people living with cancer and those who care for them.
Progress in immune oncology and drug discovery innovation offers potential for novel therapies and combinations
Immunotherapy has revolutionized the treatment of cancer. However, only a fraction of people with unique tumor features benefits from this class of therapies. Cancer cells are exceptionally adept at hiding themselves from the immune system and generating an immunosuppressive microenvironment. In fact, many tumors exhibit altered cytokine profiles and low-to-no T cell infiltration. These non-inflamed, “cold” tumors do not respond to certain immunotherapies such as immune checkpoint inhibitors.
We now see the next wave of potential cancer therapies on the horizon, propelled by significant advancements in immunology, as well as an increased understanding of tumor-driven mechanisms of immune evasion.
These new insights, together with advancement in the technologies at our disposal, may converge toward new, more targeted therapies. In addition, novel combinations of complementary therapies targeting the immune system as well as the tumor and the tumor microenvironment may offer potential alternatives for people living with cancer.
New technologies are changing cancer R&D
Just as vaccines transformed medicine over a century ago, the rapid technological advances of the past decade are changing drug discovery and development as we know it. R&D teams have access to tools to research pioneering therapeutics that would have been unimaginable just a few years ago. Progress in genomic and transcriptomic approaches are also providing insights into why an individual may respond or be resistant to therapy and are helping researchers target malignancies with potentially higher precision.
Antibodies are powerful immune proteins that recognize and bind to specific target molecules. Linking cancer-fighting small molecules to tumor-targeted antibodies gives rise to “antibody–drug conjugates” (ADCs) designed to deliver powerful cytotoxic payloads to cancer cells. Significant progress has been made over the past two decades on the design of cytotoxic ADCs. Since the first ADC approval by the FDA in 2000, a dozen cytotoxic ADCs have made it to market. Importantly, some of these ADCs can elicit an “immunogenic cell death” response, a type of cell demise that could be harnessed to enhance the activity of existing immunotherapies. More recently, a new generation of immune-modulatory ADCs are under investigation. These novel agents are being investigated to deliver molecules that can potentially localize immune stimulation at the tumor site and potentially drive immune-mediated responses to malignant cells.
Although most immunotherapies have focused on T cells, it has become clear that additional approaches are required to address the vast majority of patients that either relapse on treatment (acquired resistance), or do not experience benefit from existing immunotherapies to begin with (primary resistance). For instance, researchers are exploring the potential of natural killer (NK) cells as immunotherapies for hematologic malignancies and solid tumors. These potent cytotoxic cells are part of the innate immune system, and can identify and kill abnormal cells with a lower propensity to trigger cytokine release syndrome. Importantly, allogeneic NK cells can be obtained from healthy donors and expanded ex-vivo, making it an off-the-shelf cell-based therapy.
NK cell engagers (NKCEs) represent another emerging technology platform under investigation to redirect NK cells to the tumor. These multi-functional biologics possess a potentially tumor-targeting domain and one or two binding sites for activating receptors on the NK cell surface that can potentially boost their cytotoxicity. These NKCEs are being investigated to potentially harness the anti-tumor activity of endogenous NK cells. However, the combination of NKCEs and NK cell therapy represents an additional way to potentially impact tumor cells.
By investigating these new approaches, I believe the scientific community will be able to research and develop the next generation of immunotherapies capable of fighting cancer.
A personal commitment and many reasons for hope
The advent of new technologies is dramatically improving our ability to develop potentially practice-changing medicines for people struggling with difficult-to-treat cancers. I am excited about the potential of emerging therapeutic agents in oncology and, ultimately, our ability to possibly transform lives.
Photo: Main_sail, Getty Images