Figure 2.

Main classes of immunotherapy strategies used in neuro-oncology. Vaccine immunotherapy strategies seek to load antigen presenting cells with tumor antigens for major histocompatibility complex (MHC) presentation to T cells to activate an adaptive immune response against the antigen-expressing tumor cells. Imaging the immune response can employ PET or MR reporter-labeled antibodies that specifically recognize immune cells, or immune cells loaded ex vivo with MR or PET reporters (e.g., nanoparticles, ⁸⁹Zr-oxine) prior to injection into the subject. Cell-based immunotherapy strategies typically employ effector immune cells that are genetically modified (e.g., to express a chimeric antigen receptor [CAR]) to recognize a tumor antigen prior to re-administration into a subject. The activated cells can then proliferate and traffic to the tumor and effect tumor cell death. Imaging the immune response can employ PET or MR reporter-labeled antibodies that specifically recognize the modified immune cells, reporter gene/PET reporter probes, or cells loaded with PET or MR reporters prior to injection into the subject. Checkpoint blockade immunotherapy uses antibodies that bind to immune checkpoint proteins (e.g., programmed death-1 [PD-1]) on immune cells or the cognate proteins (e.g., programmed death-ligand 1 or 2 [PD-L1/PD-L2]) on tumor cells to prevent shutdown of cytotoxic T lymphocyte (CTL) activity by tumor cells that express these proteins. Imaging strategies can employ radiolabeled antibodies that bind to these immune checkpoint proteins. Virus immunotherapy strategies use genetically modified oncolytic or other replication-competent viruses or viral-based vectors to activate both innate immune cell (e.g., natural killer cells, macrophages) and adaptive immune cell responses against poorly immunogenic tumors. Imaging the virus can employ reporter gene/PET reporter probes, viruses with directly labeled capsids prior to injection into the subject, and other strategies used for monitoring immune responses.