What is CAR T-cell therapy?

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Dr Lucille Sarah Singh details how CAR T-cell therapy works and how it will fit in the SA healthcare system.

CAR T-cell therapy is the new kid on the block in the armamentarium of immunotherapy and cell and gene-based therapy. If nothing else, the COVID pandemic has put our immune systems under the spotlight; we have a heightened awareness of the exquisite repertoire of biological responses happening in our bodies on a daily basis to clear foreign invaders. These foreign invaders can be viruses and bacteria, but did you know that cancerous cells can also be recognised as foreign and attacked by cells of the immune system? 

A healthy immune system is theoretically meant to clear cancerous cells before they amount to a significant population. Cancer can thus arise in the setting of a dysfunctional immune system, or cancer cells may have smart mechanisms to actually evade or blunt the response of the immune system. 

The realm of immunotherapy

The front-runners of immunotherapy, being inoculation and vaccinations, are beyond the scope of this brief description. We have, for a number of years, been able to either activate or suppress the immune system in cancerous and non-cancerous diseases. In auto-immune diseases, like lupus, an overactive immune system imagines normal body cells as foreign and attacks them and immune suppressive therapies thus work. The first, and to this day, the most widely-used immunotherapeutic agent in oncology is rituximab, a chimeric antibody approved by the FDA in 1997. It’s an antibody directed against a protein on the surface of many lymphomas and harnesses the immune system to clear lymphoma cells. Rituximab can be used alone, but more so it’s used in combination with conventional chemotherapy, and potentiates the effect achieved by chemotherapy alone. 

CAR T-cell therapy

CAR T-cell therapy builds on these early achievements. T-cells are a subset of lymphocytes in our immune systems. Their job is to identify foreign cells and secrete substances to destroy them. They also recruit other role players in the immune system to come to the front line. They do this by having specialised receptors (feelers) on their surfaces. When these feelers come into contact with unfamiliar antigens (proteins) on the surfaces of foreign or cancerous cells (like a lock and key), an activation signal akin to an alarm bell is raised and the T-cell springs into action. 

The process of manufacturing the T-cells is where the magic (and unfortunately the million rand plus price tag) lies. In a nutshell the process entails:

1. Harvesting T-cells from a patient. T-cells are collected from a patient in much the same way as a blood or platelet donation. 
2. The T-cells are modified outside of the body to produce a novel chimeric antigen receptor (CAR) which is a receptor specifically designed to recognise the antigen (protein) on the cancer cells that the patient has. The modification is facilitated by allowing attenuated viruses (viruses that can’t cause infection) carrying the genetic code to make these receptors, to enter the T-cell.
3. These CAR T-cells are stimulated to divide and increase to millions of cells in the laboratory. 
4. The CAR T-cells are then infused back into the patient, just like a blood transfusion. Once these cells come into contact with cancer cells, the immune repertoire ensues, and the cancer cells will hopefully be nuked. 

FDA approval

The FDA has approved CAR T-cell therapies for certain types of leukaemias, lymphomas and multiple myeloma. Off-the-shelf CAR T-cells are also under development, eliminating the initial processes of harvesting and manipulating a patient’s own T-cells. It may be cheaper to use mass-produced donor T-cells. In addition, the landscape of cancers that may be potentially cured by CAR T-cells is expanding as research in other malignancies is ongoing. 

The health economics and historically divisive state of the South African healthcare system pose further challenges in making CAR T-cell therapy a reality locally. Having said this, we’re uniquely poised in the near future to offer the first CAR T-cell therapies in Africa. The scientific and medical community locally have published excellent insights into what is needed for a structured, controlled and quality cell and gene therapy programme in SA and are indeed making headway. We have the capabilities and infrastructure, and with some advocacy, CAR T-cell therapy isn’t a long way off.

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