Like many medical advancements, the rise of cancer immunotherapy has not been linear. As early as the 1960s, it was hypothesizedthat the body could target specific immune system structures such as cytokines, and Tcells could function to inhibit the development of cancer cells and possibly prevent them. This theory gave rise to the development of monoclonal antibodies (mAbs) for therapeutic uses in the 1970s. However, these early successes were limited. The immune responses provoked were not lasting, and many proved to be toxic. What did become apparent was that science lacked a proper understanding of relevant immune system mechanisms.
Immune checkpoints were further examined, leading to discoveries of components within the immune checkpoint such as cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and programmed cell death 1 (PD1). We know now that T-cell activity against cancer is not adequate because of the immune system’s immunosuppressive elements. To move forward, cancer immunotherapies or immuno-oncology would need to include strategies that encompassed or at least respected the effector functions, but also included negative regulators of the immune system response.
From 2010 to 2020, various immunotherapies were approved, including checkpoint inhibitors (eg, anti-CTLA4) and CAR T-cell therapies, among others. The development of these immunotherapies from discovery to market was enabled by concepts of immunoediting and a greater understanding of the tumor microenvironment (TME). Genomic profiling, immunohistochemistry, and flow cytometry also played essential roles as scientists developed endpoints to match these new realities and put more effort toward understanding toxicity to prevent immune-related adverse effects.
As we move forward into a new decade, the science around immunotherapy in cancer treatment is still evolving. New immune targets have been identified and are giving rise to new immune checkpoints, such as B and T lymphocyte attenuator (BTLA), lymphocyte activation gene 3 (LAG3), and V-domain Ig suppressor of T cell activation (VISTA). In addition, immuno-oncology is coming out of its box and becoming part of a more comprehensive and holistic cancer treatment plan that combines conventional therapies with immunotherapeutic agents.
The technology around medicine has also progressed, and those advances are not limited to oncology. Biomarkers and the data around those mechanisms are improving drug target identification, producing a greater understanding of patient stratification, and enhancing response evaluations. Likewise, tumor profiling has seen some significant developments that will continue to fuel technological advances in cancer immunotherapy. T cells that were activated and responded to a cancer cell, but were repressed by the immune system, are being tapped for new, promising treatments.
Technological advances are helpful, but they require more than scientific discovery and understanding to be useful in a clinical trial setting.Researchers should expect increased trial complexity. In some cases, this may mean selecting sites with the capabilities to support these clinically advanced trials. Still, more often, the issue will be how well the site, or even the organization running the study, is able to handle the increased volumes of data required to run these modern immuno-oncology trials. Researcher experience will come into play, as well as comprehensive adverse event reporting and data visualization to streamline studyinsights.
To read more about the lessons learned from the evolution of immune-oncology, click here to read ourwhite paper on the subject: Leveraging Lessons Learned From the First Decade of Modern Immuno-Oncology to Accelerate the Pace of Innovation in Cancer Therapy. We explore innovation within cancer therapy and describe best practices for immune-oncology going forward.