How do we teach the immune system of a cancer patient to attack cancer?

TeachableMedicalNews article 07302021

Teachable moment in classrooms:

1. cellular basis of life chapter– artificial DNA can direct the cell to make a new type of protein
2. cellular basis of life chapter – receptor proteins are located in the plasma membrane
3. tissue chapter –the liquid connective tissue nature of blood allows the separation of blood cell types
4. immune system chapter – role of T cell in immune defense

The news item:  Recently a news report was published about a cancer patient’s fight for her life:

New treatment option for patients battling aggressive form of blood cancer

People battling relapsed or refractory (R/R) Diffuse Large B-cell Lymphoma, an aggressive blood cancer, experience a challenging treatment journey. But a recently approved CAR T cell therapy gives patients a new option.

The article stated that the patient had B cell lymphoma that didn’t respond to chemotherapy, and that she started a new treatment where her T cells were removed from her blood, reprogrammed to attack her cancer, and then returned into her body.  The treatment was described as the CAR T treatment where CAR stood for chimeric antigen receptor.

So, Why Do I Care??   Some leukemia type cancers and lymphoma type cancers do not respond to regular chemotherapy. While the total number of the patients is relatively low (a few thousand), the  new approach (CAR T) to cancer treatment now presents a new option for those patients with cancers resisting regular chemotherapy. Knowing how this type of treatment is created allows us to understand treatment regimens such as Kymriah, Yescarta, and Tecartus. In addition, the CAR T treatment type may inspire more out of the box thinking to defeat cancer.

Plain English, Please!!! First, let’s talk about why would we want to train our immune system. In our body only the cells of the immune system are the only ones that can find and destroy specific targets (like cancer cells). Therefore, it makes perfect sense that when we want to destroy cancer cells, we can get it done if we train the T lymphocytes (T cells) of the immune system.

Second, let’s talk about how our T cells are trained. To bring the T cells into school, we have to take them out of the cancer patient. To harvest the T cells, the blood of the patient is continuously taken through a machine that separates the T cells from the rest of the blood components, and the rest of the blood is continuously returned into the patient.  This leukapharesis process takes  2-3 hours, then  the collected T cells are placed into cell culture, and then genetically modified. T cells recognize their target by using their receptors to grab a target molecule on the cancer cells, like a baseball mitt grabs a baseball. Through genetic modification the T cells will be given a new receptor (the chimeric antigen receptor), and the modified cells are called the CAR T cells. The new receptor will act as a baseball mitt that grabs the CD19 target molecules (the baseball) on the leukemia and lymphoma cells. When the CAR T cells bind to a cancer cell, they will destroy the cancer cells.

Third, let’s talk about how we build an army of the trained cells. To destroy millions of cancer cells we need millions of CAR T cells. Once the genetic modification is complete, the cells in culture are stimulated by cytokines to divide, and eventually to create millions of CAR T cells. The army of CAR T cells then infused back into the patient.