By CoperNick

Benedetta Spadaro

December 5, 2019

What are T cells? 

T cells are part of our immune system, they can act as a domestic police force that helps protect our body from cells that ‘go bad’. T cells detect abnormal or diseased cells by using claw-like receptors on their surface that can bind to molecules, called antigens, on the surface of cells. The detection event activates the T cells that release toxic chemicals which damage the abnormal cells and recruit other helper immune cells to make sure the abnormal cells are eliminated. 

What is the deal with cancer? 

Cancer cells are abnormal cells. They present mutations that make them different from the healthy cells, so T cells should be able to recognise and kill them. Unfortunately, this is not always the case. Cancer cells can evade the immune system and hide from T cells. The end result is that T cells are helpless and cancer cells can grow unnoticed. 

What makes CAR-T cells special?

One innovative way of targeting cancer is to equip the patient’s T cells with the right tools to detect and destroy cancer cells. This is the goal of CAR-T cell therapy. 

T cells are collected from the patient in a process that is similar to a blood donation. Cells are treated with an inactivated virus that introduces new genetic information into the T cells. The new genetic information encodes for special receptors called chimeric antigen receptors, CARs, hence the name CAR-T cells! CARs can recognise specific antigens on the cancer cells’ surface. 

The newly engineered CAR-T cells are grown in the lab in a process called expansion. CAR-T cells are then cryo-preserved and safety testing is done to make sure they are safe to put back into the patient. After expansion, millions of CAR-T cells are infused back into the patient. When inside the patient’s body, CAR-T cells act as a living drug, they can latch onto the cancer cells via the chimeric antigen receptor. Recognition of the cancer cell causes CAR-T cell activation and killing of the cancer cells. 

© 2017 Terese Winslow LLC. From: https://www.ascopost.com/issues/may-25-2018/weighing-the-cost-and-value-of-car-t-cell-therapy/

Success story: CAR-T cells can defeat cancer 

In clinical trials, an average of 3 in 4 patients with specific types of blood cancers went into remission by using CAR-T cells therapy. Interestingly, even patients who were refractory to other types of therapies responded well. in 2017, the FDA (Food and Drug Administration), approved the first CAR-T-cell therapy for the treatment of paediatric and young adult patients with relapsed and/or refractory leukaemia – a blood cancer [1].

Challenges and Future of CAR-T cells 

CAR-T cells are challenging to make. The process is expensive and has to be carried out in special conditions by highly skilled professionals. Some research groups are trying to streamline the process and build CAR-T cells banks from healthy donors and make the  ‘so-called’ Universal CAR-T cells [2]. In the future, UCAR-T cells may be purchased like other medicines without requiring extraction and engineering of each patient’s T cells. 

CAR-T cell therapy has been a real breakthrough in the treatment of some cancers. Its application has been so disruptive that several groups have tried to implement the same therapeutic approach in other types of tumours. However, CAR-T cells struggle to infiltrate in large solid tumours compared to targeting cancer cells in the bloodstream. The Cancer Research Institute has recently awarded a $1 million grant to an American group to develop a micro-chip-based model that mimics cancer cells interactions with T cells and the rest of the body [3]. This approach may help find ways to get CAR-T cells to target tumours more effectively. 

Another challenge is represented by CAR-T cells’ unique toxicity profile. CAR-T cells may overactive the immune system and cause a large inflammatory response that is detrimental to the patient’s health. This challenge is also being addressed. A standardized protocol for monitoring and handling of toxicities was recently put forward by investigators from multiple clinical institutions to form the CAR-T-cell-therapy-associated TOXicity (CARTOX) Working Group. The CARTOX criteria help doctors and other healthcare professionals manage side effects quickly and effectively. 

Overall, CAR-T cells therapies hold significant promises in the treatment of various types of cancers. If production is optimised and side effects are handled, this type of therapy could be applied safely to an increasing number of patients. This and other strategies represent a new way of battling cancer by arming the immune system to recognise cancer cells and let the body do the rest.  

For a visual explanation of CAR-T cells in action see: 

CAR T-Cell Therapy: How Does It Work? https://www.youtube.com/watch?v=OadAW99s4Ik 

CAR T-cell therapy: Reprogramming the immune system to treat cancer | Rob Weinkove | TEDxTauranga https://youtu.be/rZRsqin3lwY 

Other references: 

[1] Neelapu, Sattva S., et al. “Chimeric Antigen Receptor T-Cell Therapy – Assessment and Management of Toxicities.” Nature News, Nature Publishing Group, 19 Sept. 2017, https://www.nature.com/articles/nrclinonc.2017.148 

[2] “Manufacturing.” Cellectis, https://www.cellectis.com/products/manufacturing 

[3] Martins, Ines. “Cancer Research Institute Names $1M Technology Impact Award Winner.” Immuno,10 July 2017, https://immuno-oncologynews.com/2017/07/10/cancer-research-institute-awards-1-million-to-fund-development-of-innovative-microchip-based-research-models-of-organ-specific-cancer-immunotherapy/

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