The new era of cancer treatment: ‘Living Drugs’

By Alberto Conti, University of York

**Figure 1** | Scanning electron microscopy of pancreatic cancer cells growing in culture.

Cancer is arguably the most well-studied disease in modern medicine and yet, tackling it still represents an immense challenge for scientists across the world. In part, this is due to all of the existing types and subtypes (over 200). Cancer represents a spectrum of diseases rather than just a single disease, meaning that finding a common cure is extremely challenging. But what all cancers do have in common is their remarkable capacity of “impersonating” healthy cells.

But how do cancerous cells do this? And why exactly does it matter? This is the focus of the theory of immunoediting. The immune system has the (astonishing) ability of recognising certain biomarkers – like proteins – expressed in cancerous cells. This not only prevents their proliferation, but also promotes their eradication. Nonetheless, this process is not perfect (if it was, cancer wouldn’t be a big deal), because random mutations in cancer cells can lead to the emergence of cells with decreased immunogenicity (meaning they are less likely trigger an immune response). Over time, this Darwinian-like selection allows those cells ‘invisible’ to the immune system to thrive, leading to what we know as cancer.

**Figure 2** | Diagram showing the structure of a CAR receptor (left) and an antibody (right). The single-chain variable fragment (scFv) in the CAR receptor is obtained by linking the two chains of the variable region in the antibody (however, the scFv still retains the same specificity as the variable region).

Until recently, the only possibilities for treating this disease (when surgery was not viable), have been the use of physical and chemical based targeting of cancer cells through radio and chemotherapy. But our increasing understanding of biology, together with technological advancements, are allowing us to go a step further. What if we could harness the power and specificity of our own immune system? What if we could enhance them?

The field of study focused on answering these questions is known as immunotherapy, and one of the most promising immunotherapies to date is the Chimeric Antigen Receptor (CAR) T cell therapy. This therapy aims to modify T cells (cells in the immune system responsible of ‘coordinating’ the immune response) with CAR receptors – hybrids between receptors already present on these cells and antibodies specific to a protein of interest (Figure 2). This would allow a customised immune response to any of the cancer proteins, giving rise to a ‘living drug’.

Further modifications can enhance this therapy even more, the addition of two different, complementary CAR can increase its specificity, and incorporating ‘suicide genes’ allows scientists to terminate the treatment at any time. But even more exciting is the idea of bringing these modifications to stem cells to produce an ‘unlimited’ source of CAR T cells.

However, as good as immunotherapy might be, it also comes with certain drawbacks. For instance, costs are still huge, side effects can still represent a major problem, and perhaps the most important, it shows low efficacy against solid tumours, meaning only blood cancers can be targeted. But research is ongoing and scientists work day and night to make this therapy cheaper, safer and more effective, not only against other types of cancer but even against other types of diseases (Figure 3).

**Figure 3** | Diagram showing the principle behind CAR T cell therapy. 1) T cells are taken from the patient. 2) T cells are transfected with an inactivated virus (referred as “vector”) that contains the genes of interest (e.g. gene coding for CAR, suicide genes, etc…). Inactivated retroviruses (like HIV) are commonly used due to their ability of integrating genes permanently within the genome of the transfected cell (other ways of carrying out this step also exist, but this is the most common method). 3) CAR receptors in modified T cells are expressed. 4) CAR T cells are re-introduced in the patient. They are now specific against a chosen biomarker.

Immunotherapy is not something to hope for the future, it is already here. Clinical trials are already taking place and results have shown to be very promising, and lives of patients have already been saved. So while time and research are still needed, defeating cancer is no longer a dream. It is a goal.

About the author
I am a third-year undergraduate student at the University of York, currently in a placement year in GlaxoSmithKline. I work within the Immunoinflammation department, focusing on the role of dendritic cells in autoimmune diseases. When I’m not in the lab, I enjoy learning stuff like guitar or programming. I also play American Football, and am practising how to avoid being tackled.