Boosting the immune system to treat brain cancer

A-New-Approach-for-Treating-Brain-CancerResearchers identify mechanism implicated in brain cancer and a drug that decreases brain tumor growth.

Researchers at the University of Calgary’s Hotchkiss Brain Institute (HBI) have made a discovery that could lead to better treatment for patients suffering from brain cancer. Despite current treatment strategies, the median survival for patients with the most aggressive brain cancer – called glioblastoma, is 15 months. Less than five per cent of patients survive beyond five years.

HBI member V. Wee Yong, PhD and research associate Susobhan Sarkar, PhD, and their team including researchers from the Department of Clinical Neurosciences and the university’s Southern Alberta Cancer Research Institute, looked at human brain tumour samples and discovered that specialized immune cells in brain tumour patients are compromised. The researchers took this discovery and, in an animal model, identified a drug that is able to re-activate those immune cells and reduce brain tumour growth, thereby increasing the lifespan of mice two to three times. Their discovery will be published December 8th in the prestigious journal Nature Neuroscience.

Our brains normally contain specialized cells, called microglia, that defend against injury or infection. “Microglia are the brain’s own dedicated immune system,” explains Yong. “And in this study, we have formally demonstrated for the first time that these cells are compromised in living brain tumour patients.” As with other forms of cancer, brain tumours start as individual stem-like cells – called brain tumour initiating cells (BTICs). These cells quickly divide and grow, eventually forming a mass, or tumour. Yong and his team have discovered that the tumour disables microglia, permitting the rapid proliferation of BTICs, which ultimately leads to brain tumour growth.

“We refer to this as the battle for the brain, in which early on in the disease, the microglia are trying to destroy the brain tumour initiating cells,” says Yong. “But over the course of time, the tumour disables the microglia and we start to see more initiating cells and more rapid tumour growth. We have sought to tip the battle in favour of the brain to suppress the tumour.”

In addition to discovering this mechanism, Yong and Sarkar also identified a drug – amphotericin B (AmpB) – to reactivate microglia that in an animal model, showed a significant reduction in brain tumour growth. “This drug was able to re-activate the disabled microglia,” says Sarkar, “thus restoring the body’s natural defense mechanisms and restricting the growth of brain tumour initiating cells.”

The drug they identified is a powerful agent that is already used clinically to treat severe fungal infections of the brain and spinal cord. “It’s a rather harsh medication,” says Yong. “But we have demonstrated that this drug can be used in very small doses where it is not only well tolerated, but it is also effective in re-programming microglia.” Yong and Sarkar hope this discovery will lead to clinical trials and ultimately to a new standard of care for brain tumour patients.

The finding has already garnered attention from researchers across Canada, including internationally recognized brain tumour scientist and neurosurgeon Dr. James Rutka. “This research is highly significant as it implies that a commercially available drug, amphotericin B, which has never been used before for patients with gliomas, may be a novel treatment to consider in future trials of patients with this frequently lethal cancer,” says Dr. Rutka, Professor and Chair, Department of Surgery, University of Toronto.

The funding was provided by Alberta Innovates – Health Solutions/Alberta Cancer Foundation. V. Wee Yong is a Canada Research Chair in Neuroimmunology.

Source: Innovations Report

New possibilities for leukemia therapy with novel mode of leukemia cell recognition

Leukämie

Scientists at A*STAR’s Singapore Immunology Network (SIgN) have discovered a new class of lipids in the leukemia cells that are detected by a unique group of immune cells. By recognizing the lipids, the immune cells stimulate an immune response to destroy the leukemia cells and suppress their growth. The newly identified mode of cancer cell recognition by the immune system opens up new possibilities for leukemia immunotherapy.

 Leukemia is characterized by the accumulation of cancer cells originating from blood cells, in the blood or bone marrow. Current treatments for leukemia largely involve chemotherapy to eradicate all cancer cells, followed by stem cell transplants to restore healthy blood cells in the patients.

In a recent study reported in the Journal of Experimental Medicine (JEM) online, the team co-led by Dr Lucia Mori and Prof Gennaro De Libero identified a new class of lipids, methyl-lysophosphatidic acids (mLPA), which accumulate in leukemia cells. Following which, the team identified a specific group of immune cells, described as mLPA-specific T-cells that are capable of recognising the mLPA in the leukemia cells. The detection triggers an immune response that activates the T cells to kill the leukemia cells and limits cancer progression. The efficacy of the T cells in killing leukemia cells was also demonstrated in a mouse model of human leukemia.

Thus far, only proteins in cancer cells have been known to activate T cells. This study is a pioneer in its discovery of mLPA, and the specific T cells which can identify lipids expressed by cancer cells. Unlike proteins, lipids in cancer cells do not differ between individuals, indicating that the recognition of mLPA by mLPA-specific T-cells happens in all leukemia patients. This new mode of cancer cell recognition suggests that the T-cells can potentially be harnessed for a leukemia immunotherapy that is effective in all patients.

“The identification of mLPA and its role in activating specific T cells is novel. This knowledge not only sheds light on future leukemia studies, but also complements ongoing leukemia immunotherapy studies focusing on proteins in cancer cells,” said Dr Lucia Mori, Principal Investigator at SIgN. “Current treatments run the risk of failure due to re-growth of residual leukemia cells that survive after stem cell transplants. T-cell immunotherapy may serve as a complementary treatment for more effective and safer therapeutic approach towards leukemia.”

Professor Laurent Renia, Acting Executive Director of SIgN, said, “At SIgN, we study how the human immune system protects us naturally from infections. We engage in promising disease-specific research projects that ultimately pave the way for the development of treatments and drugs which can better combat these diseases. A pertinent example will be this study; this mode of immune recognition of leukemia cells is an insightful discovery that will create new opportunities for immunotherapy to improve the lives of leukemia patients.”

Source: The Journal of Experimental Medicine