Brain Tumor Immunology and Immunotherapy Program

About the Program

Given the seismic impact of immunotherapy in cancer over the last decade, there is tremendous enthusiasm regarding the potential for immune-based therapies in the treatment of brain tumors including glioblastoma. However, there are still no FDA-approved immunotherapies for these disease. It is likely that specific anatomic features of the CNS, the powerful immunosuppressive programs associated with brain tumors, and multi-level tumor heteroegeniety – among others – all combine to present unique challenges necessary to overcome to drive immunotherapies forward. We are passionate and motivated to reveal new insights into the the immune response to brain tumors, to develop innovative new immunotherapies for patients, and to cultivate an exciting, supportive, and mentoring community.

Our Research

• Fundamental immunobiology of the anti-tumor immune response: The immune response in the central nervous system can be considered “immunologically specialized”. Key ongoing work relates to the nature of T cell specificity and priming, the mechanisms and locations of antigen presentation, the characterization of skull and meningeal biology, and the intersection of immunity with cancer neuroscience.
• Cell therapy: Cell therapy for brain tumors involves using modified or natural immune cells—such as T cells, NK cells, or dendritic cells—to target and destroy tumor cells in the brain. Approaches include CAR T cell therapy, which engineers T cells to recognize tumor-specific antigens, and adoptive transfer of tumor-infiltrating lymphocytes or T cell receptor engineered T cells. We have developed field-leading expertise in CAR T cell approaches for patients with a range of CNS tumors.
• Cancer vaccines: Therapeutic vaccines are designed to clonally expand T cells to kill tumor cells. We have developed personalized vaccine programs to treat patients with GBM and are investigating optimal routes, methods, and combination therapies to maximize immunologic and clinical effects.
• Oncolytic virus immunotherapy: Oncolytic viruses are genetically modified viruses that both selectively infect and eliminate brain tumor cells while also stimulating the immune response to brain tumors. Significant ongoing preclinical and impactful clinical trial efforts are helping us understand how patients benefit from these approaches.
• Brain tumor immunogenomics: We are interested in the application of sophisticated genomics approaches in studying the tumor-immune system interaction. These approaches integrate profiling approaches including whole-exome sequencing, single-cell RNA sequencing, and spatial transcriptomics approaches to explore tumor cell states and their influence on immune infiltration, neoantigen discovery, and cell-cell interactions.

Milica Lukica, Program Administrator (mlukic@mgh.harvard.edu)