Q&A: The potential of immuno-oncology - a view from the R&D department
But looking beyond the headlines, what is the true potential of this emerging treatment, and where are we seeing innovations? BioPharma Reporter caught up with Dr Robin Knight, CEO and co-founder of IN-PART, an online partnering platform facilitating industry-academia collaboration, to find out more.
BPR: What are the key approaches being explored in this field?
Immune checkpoint inhibitors have already shown remarkable success in treating various cancers, including melanoma, lung cancer and bladder cancer. They’ve already significantly improved overall survival and long-term responses in some patients. Under this umbrella are two main types of therapy: Chimeric Antigen Receptor (CAR) T-cell therapy and Tumour-infiltrating lymphocyte (TIL) therapy.
CAR works by modifying a patient’s own T cells in the laboratory to express a synthetic receptor called a chimeric antigen receptor (CAR). 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). 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.
BPR: Where have some of the key innovations taken place?
We’ve already seen a number of real-world applications in the field of immuno-oncology. CAR-T cell therapy has already transformed the treatment of blood cancers, 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.
It's also been applied to treatment of prostate cancer. A leading strategy for treating this type of cancer relies on targeted androgen deprivation therapy (ADT). However, patients can develop resistance due to a mechanism driven by the pro-inflammatory cytokine interleukin-23 (IL-23). R&D teams have been able to develop IL-23 inhibitors that specifically target refractory prostate cancer to address this resistance mechanism. This raises hopes for better outcomes for patients with advanced, castration-resistant prostate cancer.
The current treatments for numerous cancer types cover a myriad of 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. Collaborations between university researchers have led to the identification of a promising series of MABs that have significant immuno-oncology implications. 18 years of data collection have led to a series of specially selected MABs that target proteins secreted by several types of cancer cells, including breast, ovarian, colon and pancreatic.
BPR: What are the limitations of immuno-oncology?
Immuno-oncology has shown great promise, but it also has a few limitations which require further investigation to navigate. Firstly, not all patients react equally to the treatments. Factors such as immune system dysfunction, tumour heterogeneity and the presence of immune-suppressive mechanisms can all lead to variability in treatment outcomes. Toxicities and side effects can also affect therapies.
There are more personalised approaches coming to the fore thanks to genomics and biomarker research, which will enable tailored treatments to individual patients based on their tumour characteristics, immune profiles and genetic makeup. 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.
Immuno-oncology also involves some persistent challenges that researchers are looking to overcome. Cancer can relapse or progress due to the ability for cells to develop resistance to treatment over time, despite an initial positive response to the therapy. R&D teams are hard at work exploring how combination therapies, immunomodulatory agents and strategies can help to reprogram the immune system to overcome resistance.
From a practical perspective, R&D teams also face challenges in bringing these kinds of treatments to clinical trials. As to be expected with the high costs associated with this kind of research, teams face ethics issues and smaller available pools of individuals to join trials. This is where there’s power in communities coming together globally, across both industry and academia, to develop and fund the trials of these treatments to unlock new progress.
BPR: What does the future hold for immuno-oncology?
It’s an exciting time in the field, as immuno-oncology treatments are set to expand due to the development of novel immunotherapeutic strategies. This includes the exploration of bispecific antibodies, immune agonists, adoptive cell therapies beyond CAR-T cells and the use of microbiome-based interventions to modulate immune responses. New treatments are possible with these innovations and can broaden the scope of immuno-oncology, which could have a huge impact on individuals.
Beyond cancer treatment, immuno-oncology in the coming years could be applied to autoimmune disorders, infectious diseases and regenerative medicine. Its future will be characterised by a multidisciplinary approach, personalised treatments and a deeper understanding of the interactions between the immune system and cancer. Further research will be key to unlocking new possibilities and improving health outcomes, as will strong partnerships and linkages between industry and academia to get discoveries out of labs and onto the market.
