The history of immunotherapy in tumor suppression dates back to the early 1900s when the pioneer of the field, Paul Ehrlich, in his study of antibody side chains suggested that molecules that react with tumors could play a key role in cancer therapy. Paul Ehrlich would go on to win the Nobel Prize in Physiology or Medicine in 1908 for his hypothesis of “immune surveillance,” which proposed that the immune system is capable of suppressing tumor formation. Fast forward 100 years and countless scientific and technological advancements later, the field of immunotherapy is an area that continues to play an ever-increasing role in the understanding and treatment of cancer.
Credit: Anna Tanczos. Wellcome Images, images@wellcome.ac.uk, images.wellcome.ac.uk
Immunotherapies either enhance the activities of specific components of the immune system or neutralize signals produced by cancer cells that suppress immune responses. An example of enhancing immune system response is exemplified in the 2015 United States Food and Drug Administration (FDA) approval of elotuzumab (Empliciti®) for patients with multiple myeloma. Elotuzumab targets the SLAM7 receptor, which is present on both myeloma cells and the immune system’s natural killer (NK) cells. By attaching to the myeloma cells, it marks them for destruction, and by attaching to NK cells, it primes the immune cells to search for and attack the myeloma cells [1].
An example of neutralizing cancer cell signaling that suppress the immune system is the inhibition of the PD-1/PD-L1 ligand-receptor complex, also known as an immune checkpoint blockade. Tumor cells secrete PD-L1, which inactivates the immune cell response when bound to its complementary T lymphocyte receptor, PD-1. A normal braking mechanism that typically prevents autoimmunity is opportunistically hijacked to promote tumor growth. Blocking this signaling should enhance immune response to tumor cells, a concept that has been demonstrated in clinical trials where a PD-1-specific monoclonal antibody induced frequent tumor regression in advanced melanoma, renal cancer, lung cancer, and colon cancer with very low rates of toxicity [2]. The FDA recently approved anti PD-1 drugs pembrolizumab (Keytruda®) for non-small cell lung cancer and nivolumab (Opdivo®) for metastatic renal cell carcinoma, Hodgkin lymphoma and melanoma [1].
These recent advances in immunotherapies are appropriately coupled with the emergence of accompanying diagnostics that will help guide clinicians in making the most precise decision. An example is the recent FDA approval of the Ventana PD-L1 (SP142) assay as a complementary diagnostic to provide PD-L1 expression status on patients with metastatic urothelial cancer who may be candidates for the FDA approved Roche immunotherapy Tecentriq™ (atezolizumab). A clinical trial showed higher overall response rates in individuals with medium to high expression of PD-L1, based on scoring algorithms developed [3].
This is the future of medicine, precision medicine: Accurately diagnosing a patient’s disease down to the very genetic and molecular profile and exploiting the tumor cells’ survival mechanism as an avenue for therapy. Limiting side effects from a medication by decreasing toxicity. Reducing patient health and financial burden through appropriate prescription of therapies that been clinically proven to be effective for the individual tumor phenotype.
Ogaga Ojameruaye is a medical student at The University of Arizona College of Medicine – Phoenix. He completed his BS in physiology at The University of Arizona and completed his MS in psychology at Grand Canyon University. Ogaga is passionate about translational medicine, bench-to-bedside research, and the discovery of new diagnostic tools as they contribute to the model of precision medicine.