by Mark Gelder, MD, Chief Medical Officer, Pierian Biosciences

Nash-news-logoIn late February, the American Society of Clinical Oncology (ASCO) partnered with the Society for Immunotherapy of Cancer (SITC) to host the first ASCO-SITC Clinical Immuno-Oncology Symposium, held in Orlando. We learned about the leading clinical research regarding immunotherapy (IO) treatment and the gradual move from IO research to actual patient application.

Immunotherapy uses the body’s immune system to help fight cancer. In the last five years, research has proven that manipulation of the immune system can control, or in some cases, completely eradicate tumors.[1] ASCO is in alignment with this new area of oncology, most recently illustrated by the success of their inaugural immunotherapy symposium.  As chemotherapy, radiation, and surgery are used to aggressively destroy cancer cells and tumors, with IO, researchers are working to develop strategies to harness the body’s own immune system to combat cancer.  When the immune system is strengthened, risk on the patient’s long-term health is reduced in comparison to more aggressive cancer treatment approaches.[2]

When IO therapy is combined with traditional treatment approaches, the potential for positive outcomes accelerates substantially[3]. Researchers have been testing immunotherapy as one component in dual combination cancer treatment. At ASCO’s symposium, many presenters mentioned the theory of the “abscopal effect” (ab meaning “away from,” and scopus meaning “target”), a term coined in the 1950s to describe the phenomenon when treating metastatic cancer with radiation. The abscopal effect occurs when the localized treatment of a tumor causes not only a shrinking of the treated tumor, but also a shrinking of other tumors outside the scope of irradiated area.[4] A 2015 clinical trial, conducted by EB Golden and colleagues, demonstrated that abscopal responses were consistently detected in patients treated with the combination of radiation therapy and immunotherapy.[5] In practice, a breast cancer patient receiving IO combined with radiation has been shown to demonstrate a positive response on a spinal lesion or other location in addition to the irradiated tumor. Researchers theorize that radiation primes the immune system to recognize tumor-specific targets as those cells die, which is then translated into a systemic effect.[6]

A concept similar to the abscopal effect is also being researched when combining chemotherapy and immunotherapy. To change the tumor’s microenvironment, researchers are using doses of chemo to destroy cells that are blocking the immune system from functioning, instead of using the dosage required to kill cancer cells. This process converts the unresponsive cells to responsive, allowing immunotherapy to work effectively.[7]

But knowing how much chemo is enough to kill the cells blocking the immune system, yet not so strong that it wipes out the body’s defense mechanism, is always difficult to assess. Questions remain: If someone were able to determine the correct dosage, would that be the same for all patients? Which patients would respond better to a combination of immunotherapy plus chemotherapy as opposed to those who would fare better with one treatment or the other? When considering the strength of chemotherapy, oncologists have zero wiggle room to take chances.

At the symposium, industry leader Lisa Butterfield led a session on “Immune Biomarkers in the Blood” featuring research findings on immune biomarkers and their ability to offer insight into the interactions between the immune system and cancer. These interactions can help to define which immunotherapy should be selected to best defend the body using its immune system.

The current research focus is on finding markers that suggest a patient will respond to any immunotherapy (IO), rather than using the biomarker to determine which IO would work best for their specific tumor and cancer[8].

gelderThe more we know, the better the outcome. There is promise in functional assays to determine the best approach to cancer treatment, including one we’ve recently developed. Our latest assay, ImmunoINTEL, identifies biomarkers in a tumor to allow oncologists to accurately personalize cancer treatment based on biology. The assay delivers the intelligence needed to determine which treatment or combinations of treatment will be most effective based on a patient’s actual tumor response in the lab, before introducing the treatment to the patient.

With assay results driving the treatment regimen, patients can be protected from the risk they would encounter if aggressive treatments had been executed prior to running the assay. A functional assay can more precisely predict a cancer treatment outcome, cut costs by eliminating ineffective treatments, and improve the quality of the selected treatment(s), resulting in a more effective and successful treatment experience from day one.

Mark Gelder, MD is Chief Medical Officer for Pierian. An experienced researcher and clinician, Dr. Gelder is board certified in Internal Medicine, Obstetrics and Gynecology. He is currently a fellow in the American College of Obstetrics and Gynecology.

[1] Ribas, A. N. Releasing the Brakes on Cancer Immunotherapy. Engl J Med. 2015; 373:1490-2. Retrieved from: http://www.nejm.org/doi/full/10.1056/NEJMp1510079

[2] Winslow, R. Cancer’s Super-Survivors/How the Promise of Immunotherapy Is Transforming Oncology. Wall Street Journal. Dec 4 2016.

[3] Disis, M.L. & Kaufman, H.L. Cancer Immunotherapy: The End of the Beginning or the Beginning of the End. Ummunsym.org Daily News, published February 17, 2017.

[4] Mole, R.H. Whole body irradiation; radiobiology or medicine? Br J Radiol 1953; 26:234-41. 10.1259/0007-1285-26-305-234

[5] Golden EB, Chhabra A, Chachoua A, et al. Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with metastatic solid tumours: a proof-of-principle trial. Lancet Oncol 2015;16:795-803. 10.1016/S1470-2045(15)00054-6

[6] Carolson, R. H. (2016, June 27) Immunotherapy ‘Plus’: Adding Radiation and Chemo to Immune Therapies. Medscape Oncology [Online]. Retrieved from: http://www.medscape.com/viewarticle/865242

[7] Thaker, P. H. (2017, February). Phase I study of the safety and activity of formulated IL-12 plasmid administered intraperitoneally in combination with standard neoadjuvant chemotherapy in patients with newly diagnosed advanced stage ovarian cancer. Poster session presented at the ASCO-SITC Clinical Immuno-Oncology Symposium, Orlando, FL.  Retrieved from: http://meetinglibrary.asco.org/content/178595-194

[8] Nyberg, K. (2017, February 24). Leveraging Immune Biomarkers in the Blood to Guide Immunotherapy—Current Application and Future Prospects [Daily News]. Retrieved from http://immunosym.org/daily-news/leveraging-immune-biomarkers-blood-guide-immunotherapy-current-application-and-future

 

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