The Breakthrough: Immunotherapy and the Race to Cure Cancer

Author: Charles S. Graeber 

We are at an inflection point in the race to cure cancer. As of June 2018, there are roughly 1000 new immunotherapy drugs for cancer that are being tested for FDA approval. In addition to this, thousands of pre-clinical phase experiments are being conducted in the field of immuno-oncology. The sheer volume of this is unprecedented and is a good indication that we are on the cusp of some big breakthroughs in the race to cure cancer.

Given the volume and complexity of the subject, I assumed this book would be full of medical jargon and a pain to read. But boy was I wrong. Charles S. Graeber has included stories of early pioneers and patients to bring out the drama in the discovery of these new breakthroughs. There are good luck stories that will leave you overjoyed with the new discoveries, and hard luck ones that are probably more common in today’s fight against cancer. This book is a must read for anyone trying to get a handle on the latest and greatest breakthroughs in the race to cure cancer.

One of the reasons I blog is to write down some points that will help me recall the details at a later date. What follows is an explanation of the key concepts and you can skip it if you plan to read the book. 

There are two distinct types of leukocytes or white blood cells in our body.  B cells, come from bone marrow  and T cells arise from the thymus. B and T cells recognize invaders by the shape of molecules - antigens - on the surfaces of the foreign bodies.  B cells generate antibodies that stick to antigens on the surface of the invaders, stopping them in their tracks while the T cell’s specialty is to recognize a compromised body cell (e.g. through a virus infection) and then kill it. 

Given the above defense mechanism, you would expect the T-cell to recognize a cancerous cell and kill it. However, this clearly is not happening in most cancer patients and their malignant tumors grow uncontrollably, eventually destroying vital organs in the body. It turns out that there are a few safety mechanisms in play that the cancerous cell uses to halt the T-cells in their tracks.

The first one is called CTLA-4 (cytotoxic T-lymphocyte-associated protein#4). This is one of the checks and balances in our immune system. It is a safety mechanism to prevent our T-cells from going into overdrive and destroying normal body cells; something that happens with auto-immune diseases. A cancerous cell has evolved to generate CTLA-4 thus holding back the T-cells from attacking them. One of the new treatments for cancer is to block CTLA-4 unleashing the fury of the T-cells on the cancerous growth. Often this resulted in the tumors melting away in a matter of days or weeks. Unfortunately, blocking CTLA-4 can cause major side-effects for people with a hyper-active immune system. In some cases this could result in serious bodily harm and even death. 

The discovery of CTLA-4 encouraged researchers to search for other checkpoint inhibitors and they soon identified a new one called PD-1, short for programmed death. This name turned out to be a misnomer, but it is an antigen on the T-cell surface that has a ligand pair, PD-L1 that is found on the cancerous cell. The PD-1/PD-L1 pair is like a secret handshake used by the cancer cell to convince the T-cell not to kill it. Blocking the PD-L1 found on the tumor is an effective way to allow the T-cells to do their job and destroy the cancerous growth.  The other benefit of this treatment is that it has fewer side effects than blocking CTLA-4. 

More recently researchers are fighting cancer with “cellular therapy” which uses whole living cells as the “drug”. One of the most promising is something called CAR-T (chimeric antigen receptor T-cell).  This involves extracting T cells from the patient and then inserting designer genes in them that will generate antibodies that target the specific cancer. These are cultivated in the lab and then re-injected back into the patient. With today’s technology the round trip of this treatment can take 21 days and cost upwards of a million dollars.  Although it is prohibitively expensive and can only be used for a few patients, it is proving to be quite effective. 

Based on all of these discoveries, and the numerous trials that are underway now, the author is hopeful that we will find more effective cures for this ravaging disease.  He says, “As a group, cancer immunologists trained hard to get lucky.”  We might be on the verge of getting lucky with finding a cure for cancer.