It’s the late 1800s. You’ve been diagnosed with an untreatable form of bone cancer, and an experimental approach is your best bet. Fortunately, you’ve been lucky enough to be treated by the best of the best, Dr. William Coley: head of the Bone Tumor Service at Memorial Hospital in New York City (McCarthy, 2006). However, the course of treatment is not what you’d expect: injecting a bacterial mixture known as“Coley’s Toxins” (McCarthy, 2006).
While late 19th century hospitals were a major advancement in offering accessible medical care, they were also petri dishes offering the perfect environment for the spread of disease. Prior to the development of modern sterilization, known as aseptic technique, a bacterial infection called erysipelas, coined “St. Anthony’s Fire,” commonly plagued hospitals (Gianfranco et al, 2021). This skin infection, eventually serving as the inspiration for Coley’s toxin mixture, was named to describe both the burning sensation that patients experienced as well as the speed through which it swept through hospitals (Graeber, 2018).
In 1891, Coley was tasked with performing a surgery on a patient’s bone cancer after a similar surgery seven years prior (2006). After a successful surgery, the patient fell ill with erysipelas. Although frequently fatal, the patient not only survived the infection, but his tumor shrunk significantly (2006). Coley hypothesized that there may be a connection between the bacterial infection and the rapid tumor eradication, and dedicated his career to the development of “Coley’s Toxins” (Graeber, 2018). As Coley’s experiments preceded a strong understanding of the immune system, their potential was limited. Although controversial and unethical, Coley’s contributions opened a door into curiosity about the immune system and led toa foundational understanding upon which many treatment options would be based. Today, scientists can understand that the bacterial infection was somehow activating the immune system and serving as a catalyst for a response against the patient’s cancer.
Notably, some of the greatest modern immunotherapeutic developments are checkpoint inhibitors and CAR T-cell therapy. Checkpoint inhibitors act on the cell growth and division cycle. This cycle is regulated by checkpoints that allow the body to trigger apoptosis (cell death) if the cell is too damaged to divide. But, cancer cells have mechanisms to sneak through these checkpoints, and continue to pass on their damaged DNA to create more cancer cells. Checkpoint inhibitors allow the immune system to recognize and destroy cancer cells (Eno, 2017). Conversely, CAR T-cell therapy allows for a personalized immunotherapeutic approach. In this process, a patient’s T-cells (cells that attack threats in the body) are collected and genetically modified with a Chimeric Antigen Receptor (CAR) gene specific to the patient’s cancer cells. Then, these T-cells are allowed to proliferate, and finally returned to the patient's body to fight their particular cancer cells (NIH, 2022).
Although historical procedures like “Coley’s Toxins” may seem outlandish at times, they provide the grounds for generating questions: the fabric of scientific investigation. Experiments being conducted today, although we may not fully understand their results, could provide foundational insight into the treatments of tomorrow.
References:
Cervellin, Gianfranco et al. “One holy man, one eponym, three distinct diseases. St. Anthony's fire revisited.” Acta bio-medica : Atenei Parmensis vol. 92,1 e2021008. 11 Sep. 2020, doi:10.23750/abm.v92i1.9015
Dobosz, Paula, and Tomasz Dzieciątkowski. “The Intriguing History of Cancer Immunotherapy.” Frontiers in immunology vol. 10 2965. 17 Dec. 2019, doi:10.3389/fimmu.2019.02965
Eno, Jessica. “Immunotherapy Through the Years.” Journal of the advanced practitioner in oncology vol. 8,7 (2017): 747-753.
Graeber, Charles. The Breakthrough: Immunotherapy and the Race to Cure Cancer. New York, Twelve, 2018.
McCarthy, Edward F. “The toxins of William B. Coley and the treatment of bone and soft-tissue sarcomas.” The Iowa orthopedic journal vol. 26 (2006): 154-8.
National Institute of Health. “CAR T Cells: Engineering Patients' Immune Cells to Treat Their Cancers.” National Cancer Institute. https://www.cancer.gov/about-cancer/treatment/research/car-t-cells. 10 Mar, 2022.