UCLA researchers in the Departments of Neurosurgery and Molecular and Medical Pharmacology have developed an autologous dendritic cell (DC) vaccine in combination with checkpoint inhibitors for the treatment of malignant brain tumors.
BACKGROUND:
Checkpoint inhibitor therapies, which unblock an existing immune response, or unblock the initiation of an immune response, are very effective at treating cancer in a subgroup of subjects that have existing immune responses. However, the subgroup of subjects is relatively small population constituting only approximately 25% of the cancer subject population. In addition, even in the responding population the response is not always complete or optimal. In many patients, the immune response is not robust and are considered “cold tumors.” There is an unmet need for more effective cancer therapies. In cold tumors, such as glioblastoma, the combination of a vaccine to recruit immune cells, and a checkpoint inhibitor to remove the brakes, may enhance or prolong an anti-tumor response in a subject, enable a subject to respond to a checkpoint inhibitor, or enable the reduction of the toxicity or the dose of a checkpoint inhibitor.
INNOVATION:
Dr. Robert Prins and Dr. Linda Liau in the Departments of Neurosurgery and Molecular and Medical Pharmacology have developed an autologous dendritic cell (DC) vaccine in combination with checkpoint inhibitors for the treatment of malignant brain tumors. When mice bearing well-established intracranial gliomas were treated with tumor lysate-pulsed DC vaccination and PD-1 antibody blockade, highly significant synergistic benefit was observed. The combinatorial treatment resulted in long-term survival in 40% of the animals and generated immune memory to the tumor. This novel technology constitutes a significant improvement and shows promise in the efficient and successful treatment of brain tumors.
POTENTIAL APPLICATIONS:
•Brain cancer therapeutics
ADVANTAGES:
•Induced robust glioma-specific T-cell responses that can eliminate tumors in the brain
•Enhanced survival in the mouse model
DEVELOPMENT-TO-DATE:
The study has been validated in experiments in vitro and in vivo in preclinical studies. Currently the technology is in clinical trials for brain tumors.