by: Astha Jaiswal
Until recently, there were three widely accepted cornerstones of cancer treatment- surgery, chemotherapy and radiotherapy. A combination of one or more of these approaches were used for the treatment of patients with different types of cancers. However, in the past decade, a fourth alternative treatment has gained prominence among researchers and Big Pharma alike, which is known as the immune-mediated strategies of cancer treatment. The field of immuno-oncology, which was virtually non-existent a few years back, is currently one of the most explosive fields in biotechnology.
Some would say that this isn’t a new field, as immuno-oncology concepts have been hot for many decades. However, immunotherapeutic agents had very little success in the clinic earlier as the techniques of immune modulation were not effective in vivo (in a living organism). The increasing knowledge of the immune system and its checkpoints has turned things around. The immune-based therapeutic approach harnesses the power of our body’s own immune system for the specific destruction of tumors. Both the innate and adaptive immune systems are known to recognize tumors, and their development can be stopped or controlled through a process known as “immunosurveillance”. It is this intrinsic ability that researchers are now manipulating in two ways: (a) enhancing tumor immunity by blocking inhibitory pathways, such as antibodies against cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed death 1 (PD-1) or its ligand programmed death ligand 1 (PD-L1), or (b) enhancing the specificity of antitumor immunity by inducing the expansion of T cells and antibodies directed to well-defined tumor antigens, such as cancer vaccines, adjuvants, and immunostimulatory cytokines.
Monoclonal antibody (mAb) based therapies have been around for some time now. Researchers are now using mAbs in various experimental approaches, such combining a mAb with a drugs to see if it has a greater effect, combining mAbs with parts of drugs, or creation of bispecific antibodies (one part attaches to a cancer cell and the other to an immune cell bringing the two together).
However, the most prominent approach is targeting various immune system checkpoints. The inherent function of these checkpoints to prevent autoimmune responses in the body. Cancer cells sometimes manipulate these checkpoints to prevent attacks by the immune system. A number of drugs targeting the CTLA-4 and PD-1/PD-L1 checkpoints are currently being tested in trials.
Trials based on immune-mediated therapies have been the highlights in oncology conferences such as ASCO, ESMO and SABCS, in the past couple of years. Gauging the potential of this field, venture capitalists are heavily financing smaller biotechnology firms based on immuno-oncology research; financial analysts are banking on a number of competing drugs in the pipeline; and a number of mergers are taking place between companies that are looking to synergize their immune-mediated platforms. For instance, very recently, Incyte and Agenus announced a global Alliance to develop novel immuno-oncology antibodies.
According to a recent equity research report by Leerink Swann, the current wave of late stage immune-mediated therapeutics represent a USD 40 billion-plus market opportunity, with significant portfolios at Roche, Pfizer, Novartis, BMS, Merck, Amgen, Astrazeneca, and others. Hence, the field is extremely crowded and competitive. The new business model in many of these companies is to combine their existing targeted blockbusters with immunotherapeutic drugs from their own pipelines as well as in partnership with competitors. For instance, Merck has been collaborating heavily for the anti-PD-1 drug Keytruda (pembrolizumab) to optimize the product ahead of its competitors. The company paired up with Pfizer’s Xalkori (crizotinib) for ALK-positive advanced non-small-cell lung cancer and with Amgen for its experimental cancer therapy, Talimogene laherparepvec, for the treatment of metastatic melanoma. Further, Pfizer’s failed bid of USD 120-billion to acquire AstraZeneca last summer, was also majorly because the company had its sights on AstraZeneca’s immunotherapy targeted portfolio.
Since every patient experiences a different response to tumor antigens and specific epitopes, immuno-oncology is seen as the ultimate in personalized medicine. Hence, discovery of novel predictive biomarkers to identify patients who can benefit from these therapies is also important. For instance, AstraZeneca’s biologic arm MedImmune recently acquired Definiens, a privately-held company that has pioneered a world-leading imaging and data analysis technology, known as Tissue Phenomics, which dramatically improves the identification of biomarkers in tumor tissue.
Cancer has perplexed the scientific community for decades and so far, the disease has eluded standard therapy. Meanwhile, it is heartening to see previous failures are now being used as a roadmap for new developments in therapies. Undoubtedly, immuno-oncology is one of the hottest and most competitive fields in biopharma and it would be interesting to watch out which one of the Big Pharma emerges as a leader in the field.