Immunotherapy: Cancer’s new nemesis
By: Brad Smith, PhD | June 01, 2015
Immunotherapy is one of the most promising avenues of research in the battle against cancer. This treatment path uses small molecules and biologics to harness a patient’s own immune system to fight the tumor – a novel approach that is poised to revolutionize cancer treatment.
This promise has been a long time coming. Scientists in the cancer research world have been working on immunotherapy treatments for decades, since the first observations were made about how important the immune system is in modulating and potentially killing cancer. These early realizations where made nearly a century ago, and we are only now beginning to harness the immune system in cancer therapies. Although there is no conclusive evidence that immunotherapy will be a “magic bullet” for all cancer indications and a significant patients, there is strong reason to believe it will be a dynamic treatment option going forward.
Many important discoveries have already been made that provide insight into how the immune system works and how it attacks cancer. For example, recent drug approvals take advantage of checkpoint inhibitors as a novel approach to immunotherapy. Instead of stimulating the immune system directly, checkpoint inhibitors block the built-in brakes that tumors apply to the immune system, allowing the system to continue to attack the cancer. This has been an unprecedented advance in the treatment for patients. We’ve found that generally 20—40 percent of patients will respond to this single intervention even when other treatments have failed before. Durable responses are even more noteworthy given the resistance to targeted therapies that is so often seen in oncology. Most exciting will be the results obtained in the many combination trials currently underway.
It has yet to be determined how these new immunotherapies will displace or complement existing therapies such as IL-2 treatment in metastatic melanoma. Approved in 1998, IL-2 has shown very good responses in a small group of otherwise very healthy metastatic melanoma patients. The therapy continues to be recommended with close safety monitoring by some but may be replaced with newer therapies or clinical trials for qualifying patients. In non-small cell lung cancer, combinations with existing targeted or chemo therapies may address the patients that lack the defining molecular characteristics for targeted agents such as crizotinib.
And there are many other products in development that span a spectrum of mechanisms and modalities, including checkpoint regulators, immunomodulators, vaccines and cell-based therapies such as CAR T-cell approaches.
While these approaches offer encouraging new opportunities, a more complete understanding of the cellular and molecular components of the tumor-immune system interaction, including the formation of neo-antigens or new targets for the anti-tumor immune response, will be necessary for the development of rational and efficacious immunotherapies in the future.
We have yet to identify how the various immunotherapy treatments can be targeted to patient groups to achieve the greatest real-world benefits for patients. Basic research and clinical results suggest that certain treatments such as radiotherapy may induce new targets for the anti-tumor immune response. This may be in addition to the existing repertoire of the anti-tumor response determined, in part, by the tumor’s genetic alterations. We have yet to see whether immunotherapies in oncology will lead us to a precision medicine approach or broad applicability across indications and patient groups.
The current competitive landscape for immunotherapies is highly complex based on ongoing trials identified on clinicaltrials.gov and other sources. At present, competition is particularly strong in the areas of solid tumors, melanoma and non-small cell lung cancer. It remains to be seen whether classical tumor-type classifications will ultimately give way to molecular pathway-based classifications whether a new clinical development paradigm of mega-phase I studies followed by rapid registration will become established.
Going forward, a central principle is that we must remember is that the immune system does not operate separately from other biological systems in the patient, including the inflammatory system. Therefore, we may not be able to define optimal immunotherapy strategies without also considering patient comorbidities and other factors. To avoid wasted time and money, an informed approach is needed for the immunotherapy platform from the outset of development. The rapidly emerging research results describing immunotherapy targets, drug combinations and responsive patient characteristics should lead to better informed studies and more successful trial outcomes.
For more information, please download our latest whitepaper: Seizing the future in Oncology: Improving the clinical development of immunotherapies