IO. where it was. where it is. where it is going.

june 3, 2019

while immune therapy is not a new concept, today’s increasing knowledge of cancer, immunology and the tumour micro-environment is leading to smarter and more effective development of immuno-therapies to treat cancer. in less than a decade, the idea of mobilizing the patient’s immune system to combat cancer has transformed from a promising concept to the emerging standard of care of many cancer types. and continuous advances and ongoing paradigm shifts in drug development are occurring on a regular basis.

while the advances over the last decade have made a significant impact in oncology, researchers have been curious how to take advantage of the immune system to destroy cancer cells for well over a century. in 1868, german physician wilhelm busch was the first to intentionally infect a cancer patient with erysipelas and he noticed shrinkage of the malignancy and in 1891, american physician william coley followed up on his own independant observation of a long term regression of a sarcoma after an erysipelas infection.

despite the advances made throughout the last century none were as pivotal as the introduction of checkpoint inhibitors. the discovery and subsequent approval [FDA] of the CTLA-4 checkpoint inhibitor was soon followed by the PD-1 | PD-L1 checkpoint inhibitor. following the introduction of checkpoint inhibitors in 2011, the FDA has since approved over 15 different checkpoint inhibitors for the treatment of cancer. these new approvals have expanded treatment options for patients with melanoma, lung, kidney, colorectal, bladder, and head and neck cancers, as well as hodgkin lymphoma.

today immunotherapy in the cancer space has moved beyond checkpoint inhibition, and in 2017, car-t cell therapy was introduced [FDA] as a novel immunotherapy. with two car-t cell therapies now available and a plethora of clinical trials underway with different targeted proteins in discovery.

but there is still so much to discover in order to fully utilize the immune system to kill cancer cells, including vaccines, monoclonal antibodies [mAbs] and tumour agnostic therapies. new inhibitory pathways are under investigation, and drugs blocking LAG-3, TIM-3, TIGIT, VISTA, or B7/H3 are being investigated. agonists of stimulatory checkpoint pathways such as OX40, ICOS, GITR, 4-1BB, CD40, or molecules targeting tumour microenvironment components like IDO or TLR are under investigation. tumour infiltrating lymphocytes, as well as CRISPR and BITE technologies
and this is only the beginning.

there remains however, a need to identify patients in whom these treatments work best, discovering mechanisms of resistance that can be overcome, and developing better means of reducing toxicities. research has shown that checkpoint inhibitors are more effective against certain tumours that have a large number of genetic changes and those that have high levels of the PD-L1 protein. identification of predictive biomarkers to identify genetic changes and guide treatment and patient selection. further knowledge of sequencing and the use of therapies in combination- immunotherapies with other immunotherapies and other forms of therapy is still necessary to fully capitalize on the promise of immunotherapy.