David Reardon, MD
Immunotherapy’s promise as well as its challenges as a treatment for patients with brain cancer was the focus of a plenary session held November 15 at the Society of Neuro-Oncology’s (SNO) 2014 Annual Meeting in Miami Beach.
Immunotherapy is coming of age not only in general oncology, but also in neuro-oncology, noted SNO President David Reardon, MD, one of four experts speaking at the session: “When you think of immunotherapy in neuro-oncology, there’s always been some hesitancy in applying it.”
Reardon, clinical director, Center for Neuro-Oncology at the Dana-Farber Cancer Institute, explained that this is because of previous research that appeared to show the central nervous system has immune privilege; however, “new evidence suggests that this might not be true and that there is a dynamic interaction with the peripheral systemic immune system and the central nervous system,” giving immunotherapy the potential to treat neuro-oncology patients.
Vaccines under investigation within the subspecialty can be classified into three categories: tumor lysates (such as DCVax L, HSPPC-96, and Allogeneic GBM stem cell line), tumor associated antigens (ICT-107, SL-701, and IMA950), and tumor-specific antigens (rindopepimut, CMV, and NeoVax). Reardon said that the immunotherapies that are furthest along are DCVax-L, HSPPC-96, and rindopepimut, which are all in randomized phase III trials. Nearly all of the research into these treatments is ongoing, with the exception of ICT-107, which has a completed randomized phase II trial, and NeoVax, which will be studied in a phase I trial that will begin soon.
Other immunotherapeutic approaches include CAR T-cell therapies, which, Reardon said, have been shown to have a dramatic effect in patients who have failed on other therapies. “This takes T cells out, engineers them ex vivo, and gives the back to patients.”
Despite the positive findings related to immunotherapy and neuro-oncology, however, physicians and patients have some challenges to overcome, said Reardon. “These tumors adapt themselves to exploit many different mechanisms of suppressing immune reactivity.”
Additionally, patients with brain cancer tend to be significantly immunosuppressed. “Very dramatically, we see multiple mechanisms the tumor has exploited to generate a protective shield and protect itself from the immune system. These are the challenges that confront us using immunotherapy,” Reardon concluded, noting that it is likely that immunotherapy will be used in neuro-oncology in combination with other therapies, including cytotoxic therapies.
In another plenary session talk, John Sampson, MD, PhD, said the current focus on immunotherapy is a “paradigm shift” within cancer and that the idea of immune privilege does not seem as certain as it did in the past. “The idea that the blood–brain barrier is an absolute barrier is not true,” he said.
Sampson, the Dr. Robert H. Wilkins and Gloria Wilkins Professor of Neurosurgery and interim chief, Division of Neurosurgery, at Duke University Medical Center, provided several areas where immunotherapy can intervene in treatment: for the release of cancer cell antigens; cancer antigen preservation, priming, and activation; the trafficking of T cells to tumors; the infiltration of T cells into tumors; the recognition of cancer cells by T cells; and the killing of T cells.
The specificity of treatment that occurs with immunotherapy raises one concern, Sampson noted: “As we go to more tumor-specific targets, it’s wonderful, but we’re not getting to the heterogeneity of the disease.”
Future research will need to pinpoint how to optimize vaccine strategies for neuro-oncology patients, Sampson said.
The plenary session also included presentations from Gordon J. Freeman, PhD, associate professor of medicine, Harvard Medical School, who gave an overview of immune checkpoint biology and therapeutic translation, and a talk from Stephen Gottschalk, MD, director, Basic & Translational Research Division, Texas Children’s Cancer Center, on the topic of T cells as therapeutics for glioblastoma.
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