Immunotherapy's Potential in Neuro-Oncology

Immunotherapy is coming of age not only in general oncology, but also in neuro-oncology, notes David Reardon, Society of Neuro-Oncology (SNO) president. Reardon was one of a handful of experts speaking on immunotherapy’s promise, as well as its challenges, as a treatment for brain cancer at the SNO annual meeting this month.

“When you think of immunotherapy in neuro-oncology, there’s always been some hesitancy in applying it,” said Reardon, clinical director of the Center for Neuro-Oncology at the Dana-Farber Cancer Institute. This observation, he says, was based on 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,” he says, giving immunotherapy the potential to treat neuro-oncology patients.

Vaccines under investigation 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 immunotherapies that are furthest along are DCVax-L, HSPPC-96 and rindopepimut, which are all in randomized phase 3 trials. Nearly all of the research into these treatments is ongoing, with the exception of ICT-107, which has a completed randomized phase 2 trial, and NeoVax, which will be studied in a phase 1 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 whose cancers have progressed 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.

John Sampson, interim chief of the division of neurosurgery at Duke University Medical Center 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.

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.