Jim Allison: Breakthrough

 Jim Allison: Breakthrough is a documentary that follows Dr. Allison’s journey in becoming a scientist and developing the immunology drug ipilimumab. Ipilimumab is a CTLA-4 antibody drug – but what does this mean?

Protein CTLA-4 is an immune system brake.

CTLA-4 is a protein on the surface of T-cells that affects the immune system. Prior to Dr. Allison’s research, CTLA-4 was identified as an activating receptor – activating the immune response. Dr. Allison’s research changed this narrative supporting the characterization of CTLA-4 as an inhibitory receptor – stopping immune response. 

Through his new understanding of CTLA-4 Jim Allison developed an antibody drug that targets the CTLA-4 receptor, as a solution to cancer. Antibodies are proteins that bind to a receptor. The antibodies from ipilimumab bind to CTLA-4 preventing the cancer from doing so, and halting the immune system. By blocking the receptor, the immune system remains activated and attacks the cancer cells – shrinking tumors in many patients. 

In addition to the scientific process of ipilimumab, the documentary highlighted the struggles that come with innovation in an investor-driven medical market. It was incredibly fascinating, while also disheartening, to view the various barriers that accompanied the testing of a new drug and new strategy in attacking cancer such as patent competition and inapplicable FDA standards dictating failure before the full course of a clinical trial could be seen. However, such barriers also highlighted a more optimistic perspective which is the resilience of those fighting to combat cancer – many driven by personal loss. 

One of the greatest points of interest for me, was the condition of those receiving ipilimumab compared with those of chemotherapy. The documentary itself did not dive greatly into the effects of chemotherapy to highlight this contrast. Although, with even a baseline knowledge of chemotherapy the difference is apparent with those receiving immunotherapy treatments feeling much better throughout the course of the treatment not facing the massive cell death that comes with chemotherapy and results in such detrimental side effects such as fatigue, weakening of immune system, and hair loss. Additionally, there is supporting evidence that immunotherapy results in survival rates as presented in the video below. 

 

“Immunotherapy won’t replace these other three [surgery, radiation, and chemotherapy], but it can be used in combination with them to offer patients the best chance to beat their disease” (Jim Allison).

Ultimately, I found the documentary incredibly compelling. My dream career since middle school is to pursue medical research in immunology with an application in oncology stemming from mother’s experiences with cancer. Not only was this documentary incredibly relevant to the work I hope to pursue but also my past life experiences with Dr. Allison ultimately taking a position at M.D. Anderson where my mother received treatment prior to her passing. As such, the relevance of the documentary also left me with questions about the work done since the introduction of ipilimumab to the market such as at which stages the drug has a high success rate and the condition of patients in the long term.