Chimeric antigen receptor T (CAR T) cell therapy has become an important tool in the treatment of relapsed and refractory malignancy. However, it is associated with significant and unique neurological toxicities.
A multidisciplinary team of clinicians at Dana-Farber/Brigham and Women’s Cancer Center (DF/BWCC) are among the first in the nation to study this issue as a team prospectively; their findings are about to be published in the journal Brain.
Colorectal cancer remains a major health problem in the United States. It’s the third most common type of cancer and the second leading cause of cancer death.
While the incidence of colorectal cancer is decreasing somewhat in the population, it has increased by 51 percent in people under the age of 50. This trend is expected to continue, with an estimated 90 percent increase in colon cancer incidence and 124 percent increase in rectal cancer incidence by 2030.
Meningiomas and pituitary tumors traditionally have been regarded as surgically treated disease. However, some patients with these tumors face recurrence, premature morbidity and mortality. This challenge has motivated researchers at Brigham and Women’s Hospital to zero in on molecular targets that shed light on prognosis and suggest novel pathways for biological treatments.
Detection of lung cancers at an early stage, combined with advances in imaging technologies and surgical techniques, bolster the rationale for choosing VATS (video-assisted thoracic surgery) segmentectomy for patients with stage I non-small cell lung cancer (NSCLC).
Over the past 20 years, more than 100 genes have been found that cause specific lung diseases, most of which can be tested for by DNA sequencing. However, interpreting and acting upon genetic test results can be a challenging task for any physician not trained in genetics. The Pulmonary Genetics Center at Brigham and Women’s Hospital is bridging the gap by providing this expertise to patients and referring physicians and assisting them in navigating this complex new field.
According to the World Health Organization, more than half of all married or in-union women of reproductive age use some form of contraception. Additionally, the number of women around the globe who either use contraception or have an unmet need for family planning is expected to grow by more than 900 million over the next decade.
Oral opioids are regularly prescribed in the United States following cesarean delivery. But in the face of the growing opioid epidemic, the wisdom of this practice is under increasing scrutiny.
Physician-investigators in the Department of Neurosurgery at Brigham and Women’s Hospital are leading clinical trials of cutting-edge approaches for treating glioblastoma. Clinical trials are currently underway for patients with recurrent, progressive glioblastoma as well as patients newly diagnosed with high-grade gliomas as investigators pursue new treatment options to stimulate a patient’s immune system to recognize and eliminate cancer in the brain.
A Study of the Treatment of Recurrent Malignant Glioma with rQNestin34.5v.2
In a phase 1 clinical trial led by E. Antonio Chiocca, MD, PhD, chair of the Department of Neurosurgery at the Brigham, investigators are evaluating the investigational drug rQNestin34.5v.2, an oncolytic viral vector engineered from the herpes simplex virus type 1 (HSV1).
The virus has been rendered incapable of making copies of itself outside of glioma cells, and the vector is designed to preferentially infect, replicate and lyse within rapidly dividing tumor cells. Once the tumor cells are lysed, the viral particles they release can infect neighboring tumor cells, continuing the process of cancer cell destruction.
The current study is designed to test the safety of the drug and will also analyze the appropriate dosage as a possible treatment for recurrent or progressive glioblastoma. While several pharmaceutical companies are developing their own oncolytic viruses for targeting various forms of cancer, Chiocca’s team is the first to begin clinical trials in patients with glioblastoma utilizing this particular oncolytic virus. So far, the team has tested this approach in 16 patients with promising results.
“Oncolytic viral vectors are the new frontier of tumor treatment, and we are at the forefront of this trend. We are hoping to see the successes we had in the laboratory translate into marked improvements for our patients with brain tumors,” said Chiocca. “This clinical trial is the culmination of over a decade of research and testing.”
GMCI, Nivolumab, and Radiation Therapy in Treating Patients With Newly Diagnosed High-Grade Gliomas
Enrollment has recently begun for another study led by investigators at Brigham/Dana-Farber Cancer Institute will test the safety of a new combination therapeutic approach to treat patients with newly diagnosed high-grade gliomas. The approach combines the use of an immunostimulator, an immune checkpoint inhibitor and standard of care therapy.
The immunostimulatory approach known as Gene Mediated Cytotoxic Immunotherapy (GMCI) involves the use of aglatimagene besadenovec (AdV-tk) injection into the tumor site and oral valacyclovir to kill tumor cells and stimulate the immune system. Patients undergo tumor resection and receive AdV-tk injection into the wall of the resection cavity. The trial combines GMCI with nivolumab, an immune checkpoint inhibitor that may also stimulate the immune system by blocking the PD-1 immune suppressive pathway. Patients also receive radiation therapy and the chemotherapeutic drug temozolomide.
A Study of Ad-RTS-hIL-12 With Veledimex in Combination With Nivolumab in Subjects With Glioblastoma
In a third clinical trial, investigators will be testing the effectiveness of a gene therapy approach in combination with a checkpoint inhibitor for treating glioblastoma. Patients enrolled in the study will initially receive nivolumab, which is currently FDA-approved to treat other forms of cancer. Patients will undergo craniotomy and tumor resection and, on the day of surgery, will receive a single tumoral injection of Ad-RTS-hIL-12 given with oral veledimex. Ad-RTS-hIL-12 is an inducible vector that encodes interleukin-12, which can activate the immune system in the presence of veledimex. This gene therapy approach, accompanied with low-dose steroids, has been tested in a phase 1 clinical trial and found to have encouraging patient survival, when compared to the historical rate of 5 to 8 months for patients with recurrent glioblastoma. The phase 1 trial combining gene therapy with nivolumab began enrollment this summer and is actively recruiting.
“I’ve had a long-standing interest in immunotherapy and gene therapy. We’ve conducted the research and have studied these therapies in preclinical models, but my interest in moving these treatments into humans is why I am at the Brigham,” said Chiocca. “The strength of research and our close connections with the Dana-Farber Cancer Institute make the Brigham a fertile environment in which to figure out the best approach for patients.”
New Research in Nature: Neoantigen Vaccine for Glioblastoma
Chiocca and other investigators from Brigham and Women’s Hospital and Dana-Farber Cancer Institute recently published in Nature the results from a phase 1/1b trial designed to assess feasibility and safety of a personalized neoantigen vaccine for glioblastoma. The vaccine was extremely safe with no significant side effects. Co-authors from the Brigham Department of Neurosurgery extracted tumor tissue from which the personalized vaccines were developed.
“This personalized approach to creating a vaccine that can reinvigorate a patient’s immune system represents the culmination of a collaboration between experts in neurosurgery and neuro-oncology,” said Chiocca. “We’re thrilled to have played a role in this innovative work.”