Saturday, 19 May 2012

Genetically Modified T-cells in Treating Cancer

By Xinyi Nan
Imagine one day in the future, not too long from now, where each cancer patient can be given a personalised set of treatments specifically targeted at one’s unique cancer cells, thus resulting in efficient tumour regression and fast recover rate. This is where the current development of immunotherapy using genetically modified T cells is leading to.
Immunotherapy is a type of disease treatment relying on the fact that the human immune system is able to recognise pathogens and elicit immune response to protect our body against these unwanted intruders. An easy way to understand this is to think about the common vaccination we receive. T-lymphocytes, or T cells, are an important group of white blood cells that forms part of this immune system, which when activated would initiate both humoral and cell-mediated immune response. But all this is based on the activation of the T cell through a protein called the T-cell receptor (TCR), found on the cell surface. And this TCR is what scientists are focusing on.

In the case of cancer, the activation sources of the T cells are tumour antigens. With recent advance in genetic engineering, scientists are able to modify the T-cell receptors so that it can recognise and increase their affinity for certain tumour antigens, transfer them into T-cells and hence allow them to be activated upon encountering the target antigens in patients. These antigen-specific receptors can either be naturally occurring ones isolated from some patients, or the chimeric antigen receptors (CARs) which are artificially engineered receptors often derived from antibodies. These receptors are then transferred into T cells through gene transfer vectors, which in turn are introduced into the patients’ lymphocytes. Figure 1 shows the general schema of how the above process works.

Figure 1. General schema of the process of gene transfer vector construction of anti-tumour receptors. (Park, Rosenberg, & Morgan, 2011)

Melanoma so far is one of the most studied upon cancer target for T cell therapy, since it has immunogenic properties. In the recent clinical trial conducted by Paul F. Robbins and fellow researchers, the antigen NY-ESO-1, which is expressed to degrees varying from 15% to 50% in highly prevalent tumours including the breast, prostate, lung and ovarian cancer, is targeted. The antigen is also expressed in approximately 80% and 25% in patients with synovial cell sarcoma and melanoma respectively, which are the patients being studied in the trial. The patients were transferred with autologous T cell transduced with a TCR directed against NY-ESO-1 to mediate tumour regression.
Objective clinical responses were observed in ten out of the total seventeen patients. As demonstrated in figure 2, tumour regression is evident in some patients showing response lasting from 8 months to 20 months. T-cell receptors are also being genetically modified to identify other antigens in various cancer types, shown in some recent studies on the effect of the TCRs in human colorectal cancer and lymphoma regression.
The T-cell immunotherapy is an interesting and promising way of treating cancer, and the recent trials on a variety of cancers have shown different degrees of success and provide a positive outlook for this technology to be further developed.

Figure 2. Computed tomography scans showing tumour regression. Tumours are indicated by the yellow arrow. (Robbins, et al., 2011)



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