HSV1 Oncolysis-Immune Checkpoint Inhibition Therapy for Breast Cancer Meningeal Metastases
Abstract
Overarching challenge addressed: Meningeal metastasis is a devastating complication of breast cancer that results when cancer cells reach the meninges lining the brain. Their subsequent growth results in severe neurological complications as tumor burdens the cerebrum, spinal cord, and cranial nerves with debilitating consequences. As a result, patients do not survive beyond 3-4 months. It is now diagnosed more often as patients with primary and metastatic cancers survive longer with treatment advances. Aggressive treatment with radiation, systemic and local chemotherapy is accompanied with toxicities and complications. Chemotherapy is rapidly cleared by the cerebrospinal fluid, and doses that would be effective are highly toxic. Therefore, novel treatment options are eagerly awaited. Type of patients who will be helped and how: The proposed research will vastly benefit terminally ill stage IV breast cancer patients diagnosed with meningeal metastasis. Our preliminary work has shown that oncolytic HSV1 inhibits tumor meningeal metastatic growth. Our proposed project takes this information to another level to introduce immune checkpoint inhibitors together with oncolytic HSV1 to treat this resilient cancer. Clinical applications and benefits and risks: Oncolytic HSV1 and immune checkpoint inhibitors are currently used in the clinic for other cancers, although they have not been investigated as therapeutics for meningeal metastases. As they are in clinical use, they can be directly applied to patients. The benefit is insurmountable. For this disease, which has no treatment, this proposed research will provide patients with a potential treatment option with hope for a cure, extend their life expectancy, and greatly improve their quality of life. The risks are minimal. As for oncolytic HSV1, as they are replication conditional viruses, they will replicate preferentially in cancer cells as opposed to normal cells. However, in the event of unforeseen replication, there are anti-herpetic drugs such as acyclovir that can be administered. As for immune checkpoint inhibitors, they are widely used in the clinic. Projected time for patient related outcome: Since the suggested therapeutics (oncolytic HSV1 and anti-PD-1 antibody) are in clinical use, the data generated from the proposed research can be directly translated to the clinic. The current proposal, if successful, can be fine-tuned with the wealth of novel data that will be generated to be further investigated for patients with meningeal metastases. Likely impact on the Breast Cancer Research Program’s mission to end breast cancer: This research, which has the clear markings of success, will have a huge impact on patients with stage IV metastatic breast cancer. Currently there is no cure, and patients have no hope of survival beyond 4 months. The proposed research will target meningeal metastases, which are diagnosed often at the late stages of disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010421
Entities
People
- Kumudu Kuruppu
Organizations
- Massachusetts General Hospital
- United States Army