A New Model for Defeating Cancer: CAR T Cells

Joshua Kofford

BIO 1610-009

Dr. Michaela Gazdik-Stofer

February 28, 2017

Since I was little, I can remember people asking what I wanted to be when I grew up and I always responded with, “a doctor!” This still holds to be what I want to do, but I have started to narrow it down a little more. I have shown a lot of interest in the field of radiology, and have decided I want to do interventional radiology. This may change, but for now it is what I have my eyes set on. Interventional radiologist performs minimally invasive image guided diagnosis and treatments of diseases in every organ. A lot of these procedures deal with cancer in different organs. This is why I chose this article. After a close friend died from leukemia in high school, I’ve become interested in the causes, cures and preventions of this disease.

This article discusses a new form of treatment for leukemia, a cancer that forms in our blood cells. The treatment involves genetically mutating the T cell found in our immune system to target and destroy cancerous cells.

For decades, tumor immunologists have known the important role the immune system can play in fighting cancer. Early attempts to prove its potential were disappointing. Investigators had not done enough to stimulate the T, or CAR T, cells, a key component in the immune system identifying and attacking cancer cells. The immune system was not provided with enough ‘fire power’ to destroy the cancer cells.

The strategy now used and developed by this team of immunologists was discovered while searching for new HIV treatments. The T cells are “turbocharged,” after being drawn from the patients. This is done by using magnetic microbeads, infused with dendritic mimicking proteins (dendritic cells are the cells that activate the T cells). This makes the “cells more abundant, powerful and longer-acting than previous methods.” About 10 years ago, another method was discovered that is used along with this method. This method allows the T cells to efficiently home in on and attack certain kinds of cancers that stem from the white blood cells.

Even with the “turbocharged” T cells, our body still faces two major challenges when mounting an immune response to cancer. The first is that malignant cancers cells come from our own cells. Second, cancer cells “exploit various tricks to thwart an immune response.” This posed a problem, because the cancer cells could basically trick the T cells into thinking they are not a harmful cell to our body.

To get around these two major challenges, the CAR T cells were discovered, and how powerful they could be in destroying cancerous cells. The CAR T cells were altered, so that instead of picking a target based upon antigens released by all cells, they would pick an antigen released by all tumor cells, that could not be hidden. 

In 2010, after these cells were tested on mice, clinical trials were performed on 3 adult patients who had chronic lymphocytic leukemia, and were not responding to other treatments. William Ludwig was one of the first. Having been diagnosed for over 10 years, he was now carrying over 5 pounds of leukemic cells. After being injected with 1 billion of his own genetically modified CAR T cells, he soon developed a fever, low blood pressure and difficulty breathing. This was because his immune system had gone into triple overdrive in response to the CAR T cells. Ludwig did come through though, and 1 month later his doctor could find no evidence of leukemia in his body.

Tests have now been performed in children, and the researches latest results show an overall survival rate after 12 months of 62 percent, with less than 10 percent of these patients using standard treatment for leukemia after a year. There is no proven reason why some people respond to the CAR T cell treatment, and others do not. Some relapses of the leukemia have been reported, due to the fact that the CAR T cells did not multiple in the patients, or new types of leukemic cells evolved that the CAR T cells could not target. Even though the challenges have arisen, as a research community, there are still developments and tests surrounding this breakthrough.