Cancer research hinges on developing improved methods to effectively lyse cancer cells. This is where immune checkpoint inhibitors come into direct focus

Cancer research hinges on developing improved methods to effectively lyse cancer cells. This is where immune checkpoint inhibitors come into direct focus. Also referred to as immune system blockades, the biological-science community agrees that these immune checkpoint inhibitors represent one of the more important keys to effectively treating various types of cancer. Immunology has emerged within the last decade as a new isolated research discipline. Discoveries on how to improve immune function have placed immunology on the pioneering forefront. As a result, millions of dollars are being thrust into high-tech research efforts via Bio-Pharma powerhouses.

What we know about immune checkpoint inhibitors is that they are a vital component in the destruction of cancer cellsi. The research about immunity and the specific role immune checkpoint inhibitors is capturing the attention of leading oncologists. Restructuring how the immune system performs, to make the immune checkpoint inhibitors to disrupt its natural function to serve as a halting mechanism, is where the magic ends and real science talk begins.

Understanding immune checkpoint inhibitors – how they work

Because cancer cells have the ability to virtually "trick" typical immune system check-points to avoid being attacked, the researchers utilise immune checkpoint inhibitors to alter this message. Checkpoint proteins act as a braking system for the immune system. Research has found that by "switching off" the protein’s natural inclination to stop the immune response, that they can begin to fight cancer. This message also serves as a detection method to determine the cells that are normal and those of cancer. Once alerted to attack, the body's immune system is unleashed upon the cancer cells and begins to lyse them as a foreign substance. This is elementary to understanding check-point inhibitors – the realisation that they need to be given a signal to release the body’s defence system. On a more complex level, researchers dive deeper into what the best check-point inhibitors are, and dissect the unique function of each and determine its efficacy. Used in conjunction with other immuno-therapies, cancer treatments have become more optimal, for better patient outcomes.

Immune checkpoint inhibitors – new research discoveries

Research led by respected oncologist and renowned researcher, Dr. Ari VanderWalde, illustrates critical information regarding what we now know about the role of immune checkpoint inhibitors. Much of the research is reflecting that the use of checkpoint blockades are actively utilised in combination therapies to treat advanced cancer stages in instances of melanoma and other tumour-related cancers. Additionally, the use of oncolytic viral therapies further enhances the efficacy of anti-PD-1 type inhibitorsii. Of notable discovery in the use of checkpoint inhibitor disciplines, is the workmanship again by Dr. VanderWalde on MSI (Microsatellite Instability)iii. This technology works to determine the best patient identifiers for possible checkpoint inhibitor therapies. With this stunning discovery, the prognosis and patient treatment efficacy is markedly improved. The published research reflects that the correlative data from checkpoint inhibitors PD-L1 and TMB places oncologists at an advantage to offer distinctive treatment decisions for each patient.

The potential dangers of utilising checkpoint blockades in therapy

Safety and efficacy don't work in opposition of one another in cancer therapies. Oncolytic viral therapies, or combination therapies, are touted for their ability to maintain control of patient CINV and other related issues. As with most benefits of new drug discoveries, there are a handful of risks associated with use. At an annual conference, the National Comprehensive Cancer Network (NCCN) 23rd Annual Conference in Orlando, Florida, John A. Thompson, MD, of the Fred Hutchinson Cancer Research Center and the Seattle Cancer Care Alliance, spoke on the topic regarding immunotherapy-related toxicities and their management. Thompson is quoted as saying:

"The use of immune checkpoint inhibitors has revolutionised the treatment of melanoma and other cancers. But with this good news has come some not so good news: immune-related adverse events (irAEs) can cause serious harm to patients receiving these drugs."

Toxicity is the chief word of interest and concern. With the ability to destroy beneficial cells of major organs, and affect many other areas of potential harm to the body, the alarm bells get triggered easily when using checkpoint inhibitorsiv. So much in fact that there are new guidelines in place to ensure adherence to strict safety compliances. In these instances, medical experts rely heavily on benefit versus reward. The good news is that in many of the recent phase 3 trials and clinical reports, adverse effects have been minimal and patient tolerability is goodv.

Conclusion – what is the future of checkpoint inhibitors

The medical community and research continues to point out new approvals for use by the FDA in advanced staged cancers. As we head to the future, look for more studies and drugs that work on a molecular level. Ongoing trials are attempting to answer questions about targeting BRAF and related pathways. There also seems to be a push to gain more relevance through the use of "basket trials" to try innovative immunotherapy options. Recent notable approvals include:

  • Nivolumab (Opdivo), a type of immune checkpoint inhibitor used in combination therapy for melanoma.
  • Darbrafenib (Taflinar), a type of immune checkpoint inhibitor that is used with mutated cancers displaying the BRAF gene.

*There are many more CPI's approvals that are in current use being utilised in ongoing clinical trials. Those mentioned are notable and used for example for their use in anti-PD-1 Phase trials and also advanced melanoma/BRAF gene mutations.

George Clinical is a leading independent Asia-Pacific based clinical research organisation (CRO) with global capabilities differentiated by scientific leadership, innovation, and extensive investigator networks. With staff operating in 15 countries, George Clinical provides the full range of clinical trial services to biopharmaceutical, medical device, and diagnostic customers, for all trial phases, registration, and post-marketing trials. For their Oncology offerings, George Clinical works closely with scientific leaders from West Cancer Centre, a US-based leader in care and research, and combines this scientific and clinical leadership with an expert trial delivery capability to create a distinctive world-class service.



iii Microsatellite instability status determined by next‐generation sequencing and compared with PD‐L1 and tumor mutational burden in 11,348 patients


v P3.02c-102 Safety and Tolerability of AbemaciclibCombined with LY3023414 or with Pembrolizumab in Patients with StageIV NSCLC