Reprogramming the immune system for cancer therapy
Our immune system is amazing, and over the last decade we have begun to realize really just what that means. The market launch of “checkpoint inhibitor” antibodies which help the immune system recognize and attack cancerous tumors has revolutionized cancer therapy. In the process it has redefined a whole new field of medicine; cancer immunotherapy.
What is Cancer Immunotherapy?
Cancer immunotherapy is used to describe any therapeutic approach where the body’s own immune system is reprogrammed to attack and eliminate the cancer. This can be with a traditional small molecule medicine, a therapeutic tumor infecting virus, targeted antibodies, cancer vaccines, cytokines or cell therapy. What unites the approaches is the engagement of different types of immune cells from the innate and adaptive immune system to eliminate the tumor.
So what needs to be reprogrammed and how?
We are still at the beginning of our journey to understand the complexities of what immune reprogramming is necessary to address the problem.
One aspect that is now well established is that reprogramming immune cells such as T-cells can be very effective. The checkpoint “off-switches” such as PD1 and PD-L1 are used by the cancer to keep the T cells switched off. Ordinarily, T cells recognize and kill abnormal cells such as cancer cells, but cancer cells are sneaky and can switch these immune cells off. Blocking even just one of these off-switches has been shown to have miraculous results when used to treat cancer, with big reductions in tumor size and remission seen in late-stage cancers such as lung cancer and melanomas.
What’s left to do?
But checkpoint inhibitors don’t work for everyone, nor for all types of cancer. A current active area of research involves looking at all the different types of immune cells, not just cytotoxic T cells, to interrogate the reasons why only some tumors are susceptible to checkpoint therapy. The goal is to understand the underlying biology and develop second-generation medicines or combination treatments. To improve the response rates and range of cancer types that can benefit from checkpoint inhibitor treatment.
What types of immune cells and in vitro models can we study to develop the next generation of therapies?
Anyone who has looked in any depth at the immune system will know it is insanely complicated. Not only are there a lot of differences between animals and people and between different people, there are also a lot of different immune cell types to contend with. Even “T-cells” is an overly simplistic term and in the laboratory, we can characterize and study a whole range of sub-categories such as cytotoxic T-cells, exhausted T-cells, regulatory T cells, memory T cells and helper T cells. And that is just the T cells, the adaptive and innate immune system has a range of other cells which play critical roles such as tumor-associated macrophages (TAMs), dendritic cells and NK cells to name just a few.
Furthermore, the tumor itself signals to the immune cells and can alter their behavior and even what type of immune cell subcategory they are classed as. To unpick all of this we need to develop complex laboratory models with more than one cell type (a co-culture) to mimic what happens in the tumor microenvironment.
How do we know if a therapy has a beneficial effect on the immune cells we are interested in?
In a nutshell, we test it. Using cells in culture that can mimic what immune cells look like in the tumor is a great way to be able to tell if a therapy can do what we want it to do. For example, our exhausted T cell assay mimics the key features associated with exhausted T cells and can be used to test the ability of prototype medicines to switch these cells back on.
What’s the future?
To find out about some of the recent developments and new assays available for drug discovery, or if you’d like to learn more about our T-cell exhaustion or TAM assays, you can hear from Dr. Justyna Rzepecka who is hosting a webinar Biologics masterclass: immunotherapy discovery & development
Further reading