Dr. William Curry's 2018 Update for the Marcus Foundation

2018 Update for the Marcus Foundation

From Dr. William Curry

We are excited about progress that is being made in understanding and manipulating the immune system’s response to brain tumors. Amazing and successful results using immunotherapy are being reported in patients with advanced cancer; however, these therapies have not yet translated into significantly better outcomes for patients with brain tumors.

We are of the firm belief that success in treating brain tumors with immunotherapy is within reach; however, it will require more detailed understanding of how the immune system responds to brain tumors in their natural state, as well specifically targeted immune interventions – using combinations of immunotherapies, either simultaneously or in sequence.

Over the past year, support from the Marcus Foundation has allowed us to continue studying combination immunotherapies in brain tumor models in mice. We recently published a study (https://www.ncbi.nlm.nih.gov/pubmed/29016879) showing that combining a personalized and subcutaneously delivered brain-tumor vaccine with simultaneous delivery of therapeutic antibodies first activates immune cells again the tumor and then further stimulates these cells and makes the brain tumor environment more fertile for immune-based killing. The two arms of therapy work via different mechanisms, have only modest impact as single therapies, and clearly synergize when given together. We have built upon these studies by adding a third arm, intended to specifically stimulate proliferation of a particular type of activated immune cell. Early results show dramatic impacts on the survival of these tumor-bearing mice – curing essentially all of them.

This type of work serves as the foundation upon which clinical trials can be built, and seed funding from the Marcus Foundation and groups like it is essential to moving the needle against brain cancer.

Overview on the Marcus J. Niziak (Marcus) Fund for Families

The Marcus Fund for Families provides vital support to pediatric neurology patients and their families at Massachusetts General Hospital. 

This funding provided by the Niziak family is making a meaningful difference in the lives of these children and families, providing access to funds to subsidize meals, parking and other associated costs.

Many of these patients receive care over a prolonged period, placing a considerable financial burden on their families. Time away from home, other children, leave from work and the stress of illness weigh heavily on these families. The Marcus Fund for Families allows us to alleviate some of the small financial stressors that come with hospital stays. Several of our families share with us that not having to worry about small expenses that add up, such as parking, meals and other incidentals, helps make their stay more comfortable and has a huge impact during an otherwise difficult time.

We have also had instances where the Marcus Fund for Families has allowed us to significantly impact our patients day-to-day lives by supporting custom communication solutions, accessibility modifications at home or educational solutions to ease their return to school.

Having funds available to help our neediest families in this way is truly a blessing.

Overview on Dr. William Curry’s Lab for the Marcus Fund

The mission of the MGH Neurosurgery Brain Tumor Immunotherapy Laboratory is to design, explore, and translate novel approaches to manipulating host immunity against malignant brain tumors (malignant glioma). For the immune system to deter the progression of cancerous cells in the brain, we must train it to better recognize its targets and to overcome the evasive strategies that glioma cells have evolved in order to escape both immune detection and control.

We, therefore, study the mechanisms by which brain tumors evade immunity and other treatment approaches. We believe strongly in the role of combination immunotherapy strategies that increase numbers of tumor-targeting lymphocytes as well as increase the conditions that permit their prolonged activation.

In a phase I clinical study in patients undergoing surgery for recurrent glioblastoma (Grade IV astrocytoma), we have demonstrated that a patient’s own tumor cells can be harvested and used as material for a personalized cancer vaccine that positively impacts multiple arms of an antitumor immune response – both antibodies and T-lymphocytes. We have taken these data back into the preclinical setting and examined combining that vaccination with delivery of therapeutic antibodies that activate tumor-specific T lymphocytes, cells that otherwise may be suppressed by tumor-related factors. In animal models of brain cancer, we are seeing increased survival by combining vaccination with 2 or 3 of these antibodies, and our aim is to move these combination approaches into new clinical trials.

In other lines of investigation, we are studying the impact of common mutations in lower-grade glial tumors have on the immune system and whether or not these tumors are, therefore, good targets for immunotherapy. In these experiments, we are collaborating with Dan Cahill, MD, PhD and Hiro Wakimoto, MD, PhD, both of whom have significant expertise in brain tumor molecular genetics and glioma modeling.

We are also collaborating with Marcela Maus, MD, PhD in the design and evaluation of a chimeric antigen receptor (CAR) T lymphocyte that is engineered not only to specifically target and kill glioma cells but also to secrete immunostimulatory factors directly into the tumor microenvironment – hopefully increasing the both targeting efficacy and overcoming local immunosuppression.

Massachusetts General Hospital Grant

The Foundation recently provided a grant to the Massachusetts General Hospital (MGH). The proceeds were used in part to continue to fund the Marcus Fund for Families at MGH. The fund is used to help defray the cost to families with children undergoing treatment at MGH for cancer and other illnesses. The recent grant will also be used to support the research of Dr. Will Curry, the attending neurosurgeon at MGH. Dr. Curry is bringing new clinical trials forward which demonstrate that immunotherapy protocols (vaccines) can be used to supplement standard therapies in the treatment of brain tumors. Dr. Curry plans to attend this year's Marcus Foundation Golf Tournament and will provide an update on his research.

Grant to the Marcus Fund for Families

The Foundation has once again provided a grant to the Marcus Fund for Families at the Massachusetts General Hospital (MGH). The fund was established to help defray the costs  to families with children undergoing treatment at MGH for brain tumors and other neurological diseases. Moreover, we are also pleased to announce that we will be supporting the research of Dr. Will Curry at MGH. Dr. Curry is the attending neurosurgeon at MGH and is bringing new clinical trials forward which demonstrate that immunotherapy protocols (vaccines) can be used to supplement standard therapies in the treatment of brain tumors.