Dr Robin Knight, CEO and co-founder, IN-PART, discusses emerging cancer immunotherapies.
Cancer immunotherapy, also referred to as immuno-oncology, is gaining traction. New treatments are becoming available all the time, and they’re showing incredible promise in being able to treat diseases affecting thousands of people around the world.
But under the surface, what is the true potential of this emerging type of treatment, and which areas are ripest for innovation?
The science behind the innovation
In the field of immuno-oncology, the development of immune checkpoint inhibitors has been one of the leading innovations. They’ve already shown remarkable success in treating various cancers, including melanoma, lung cancer and bladder cancer, demonstrating significantly improved overall survival and long-term responses in some patients. There are two main types of therapy: Tumour-infiltrating lymphocyte (TIL) therapy and Chimeric Antigen Receptor (CAR) T-cell therapy.
Tumour-infiltrating lymphocyte (TIL) therapy acts by isolating immune cells called lymphocytes from a patient’s tumour, expanding them in the laboratory, and then reinfusing them back into the patient, with these TILs primed to recognise and attack cancer cells. Expressing a synthetic receptor called a chimeric antigen receptor (CAR) by modifying a patient’s T cells in the laboratory is key to how CAR works. The CAR is designed to recognise specific proteins on cancer cells and trigger an immune response against them. This method has proved particularly useful in treating certain types of blood cancers, such as acute lymphoblastic leukaemia (ALL) and diffuse large B-cell lymphoma (DLBCL).
Applications in the real world
Real-world applications have already come to fruition in this developing field. For example, CAR-T cell therapy has begun to play a role in transforming blood cancer treatment, but efficacy against solid tumours remains a challenge. R&D departments have made use of genetic engineering to create CD8+T cells that overexpress COBRA-1. This both increases the ability of T cells to kill cancer cells while also extending their life span by preventing T cell exhaustion and increasing the number of memory T cells.
The treatment of prostate cancer has also benefitted from immuno-oncology. Here, targeted androgen deprivation therapy (ADT) has been a leading strategy for treating this type of cancer. However, patients can develop resistance due to a mechanism driven by the pro-inflammatory cytokine interleukin-23 (IL-23). Incredibly, R&D teams have been able to develop IL-23 inhibitors that specifically target refractory prostate cancer to address this resistance mechanism. This brings fresh hope for patients with advanced, castration-resistant prostate cancer.
The existing treatments for cancers today are typically varied and fall under both biological and synthetic processes. One particularly powerful method is via the use of monoclonal antibodies (MABs). These artificially created antibodies are designed to act as a targeted drug therapy by replicating a naturally occurring antibody. Academic collaborations have led to the identification of a promising series of MABs that have significant immuno-oncology implications. Nearly two decades of data collection have led to a series of specially selected MABs that target proteins secreted by several types of cancer cells, including colon, pancreatic, breast, and ovarian.
Limitations of the approach
Immuno-oncology has shown huge potential in the treatment of diseases, but there are some existing hurdles which still need to be overcome. A big challenge that remains is that not all individuals react equally to treatments. Factors such as immune system dysfunction, tumour heterogeneity and the presence of immune-suppressive mechanisms, and even toxicities and side effects, can all lead to variable outcomes.
However, there are personalised approaches materialising. Genomics and biomarker research have helped make tailored treatments to individual patients a reality, driven by immune profiles, genetic makeups and tumour characteristics. But R&D around these approaches comes with high costs, and personalised treatments are naturally more expensive. Healthcare systems with limited resources are therefore restricted in terms of access to these innovations.
Researchers are also battling with some persistent challenges. It’s well known that cancer can relapse or progress due to the ability for cells to develop resistance to treatment over time, even in cases where an initial positive response has been shown. R&D teams are exploring how combination therapies, immunomodulatory agents and strategies can help to reprogram the immune system to overcome this.
R&D teams can also find it difficult to help push treatments to the clinical trials stage. There’s the high costs associated with this kind of research, as well as issues around ethics and the availability of individuals to join trials, with numbers often limited. This is where there’s a need for R&D communities to come together across the world to unlock new progress.
Where the future lies
Immuno-oncology looks set to take its next step as novel immunotherapeutic strategies come to fruition. For example, immune agonists, bispecific antibodies, adoptive cell therapies beyond CAR-T cells and microbiome-based interventions are now being explored. Individuals could be set to benefit from these expanding approaches and help widen the scope of immuno-oncology.
There’s even potential for treatments beyond cancers, including autoimmune disorders, infectious diseases and regenerative medicine. Most importantly, its future success will be defined by whether a multidisciplinary approach is taken, personalised treatments are adopted and the relationship between the immune system and cancer is better understood.
As a final point of note – it’s likely this will continue to be an area of focus for academic and industry collaboration, so it’s important for R&D teams to be open to exploring new partnerships to push new developments forward.
This means looking beyond some of the traditional research scouting methodologies, especially for teams where resource is limited and attending all relevant conferences and digesting new papers as journals as they are published isn’t always an option.
Technology can help close the gap here, opening the door to new academic and industry partnerships through digital calls for research or virtual collaboration capabilities. It’s an exciting time in the sector, and supercharged by the power of collaborative technology, fresh developments are sure to keep coming.
