Over the past decade, immuno-oncology (I-O) has emerged as a novel treatment approach to fight cancer.
I-O agents known as checkpoint inhibitors block immune checkpoints like PD-1 and CTLA-4, found on immune cells called T cells, or PD-L1, found on tumor cells, from suppressing the anti-cancer activity of immune cells.
By targeting these checkpoints, I-O therapies harness a patient’s own immune system to destroy cancer cells. In some cases, when compared with traditional chemotherapy and radiotherapy, I-O agents can provide more durable clinical outcomes (due to immunological memory).
While currently approved checkpoint inhibitors have dramatically improved the treatment landscape, these therapies are often only effective in a subset of patients, and those who benefit may eventually develop resistance to treatment. Both progressive tumor heterogeneity, or cancer cell mutation, and naturally occurring pathways that prevent autoimmunity can mitigate the effects of therapy over time.
Dr. Hesham Abdullah, Senior Vice President and Global Head of Oncology Development at GSK, highlights the importance of developing more therapeutic options to benefit a broader patient population:
“The critical elements here are a focus on translational science and identifying additional predictive biomarkers.”
Another key area of study is immune profiling: assessing a patient’s immune and tumor related factors that may help scientists better determine an individual patient’s likelihood of responding to I-O therapy.
GSK’s recently expanded collaboration with Tempus, an AI-enabled precision medicine company, will play a key role in enabling informed acceleration of I-O drug development through improved clinical trial design, faster enrollment and additional translational insights.
Having access to Tempus’ vast library of de-identified patient data and expansive clinical network “will no doubt help us better identify predictive biomarkers and subgroups of patients that can best derive potential benefit from novel immunotherapies,” Dr. Abdullah explains.
The CD226 axis is a particularly promising target for new I-O therapies. This co-stimulatory factor is expressed on the surface of T and NK immune cells. By developing antibodies that bind to inhibitory checkpoints CD96, PVRIG, and TIGIT, CD226 can then bind to CD155 and CD112 molecules on tumor cells, thereby increasing the anti-cancer activity of T and NK cells.
“T and NK cells continue to play a key role in an individual’s immune response. We’ve seen that the ability to improve the activity of such cells may potentially have an effect on cancer cells.”
Dr. Hesham Abdullah, Senior Vice President and Global Head of Oncology Development at GSK
“GSK aims to use human genetics and functional genomics to gain more insights into the role that certain targets may play in disease,” Dr. Abdullah explains. “We’re currently looking at genetic variants that exist around the CD226 gene and their potential interplay with immune and cancer phenotypes. This can give us confidence that we’re targeting the right checkpoints in the most appropriate way.”
GSK is uniquely positioned as the only company with access to antibodies targeting all three known CD226 checkpoints—CD96, PVRIG and TIGIT. GSK’s goal is to develop a new generation of I-O that will positively impact the future of cancer care, particularly for those patients who have not benefited from currently approved therapies.
Per Dr. Abdullah, “the focus has always been about improving long-term outcomes.” Novel combinations involving immune checkpoints such as TIGIT, CD96, and PVRIG will hopefully increase the proportion of patients who respond to therapy and improve the durability of response.
“The use of doublets (combining TIGIT or CD96 or PVRIG with PD-1) or even triplet combinations could help address unmet medical need and drive longer term benefit,” Dr. Abdullah explains.
GSK is at the forefront of innovation in R&D, building a diverse portfolio that leverages the science of the immune system. By investing in human genetics and advanced technologies through collaborative agreements with biotechnology and academic partners, GSK has made tremendous strides in I-O development. GSK will continue to build on first- and second-generation I-O research, aiming to bring novel therapies to more patients.
Learn more here.
NP-GBL-AOU-WCNT-220005 | Date of preparation: December 2022 | Funded by GSK