A successful therapeutic paradigm established historically in oncology involves combining agents with potentially complementary mechanisms of antitumor activity into rationally designed regimens. For example, cocktails of
cytotoxic agents, which were carefully designed based on mechanisms of action, dose, and scheduling considerations, have led to dramatic improvements in survival including cures for childhood
leukemia,
Hodgkin's lymphoma, and several other complex
cancers. Outcome for
glioblastoma, the most common primary malignant CNS
cancer, has been more modest, but nonetheless our current standard of care derives from confirmation that combination
therapy surpasses single modality
therapy.
Immunotherapy has recently come of age for medical oncology with exciting therapeutic benefits achieved by several types of agents including
vaccines, adoptive T cells, and
immune checkpoint inhibitors against several types of
cancers. Nonetheless, most benefits are relatively short, while others are durable but are limited to a minority of treated patients. Critical factors limiting efficacy of immunotherapeutics include insufficient immunogenicity and/or inadequate ability to overcome immunosuppressive factors exploited by
tumors. The paradigm of rationally designed combinatorial regimens, originally established by cytotoxic
therapy for oncology, may also prove relevant for
immunotherapy. Realization of the true therapeutic potential of
immunotherapy for medical oncology and neuro-oncology patients may require development of combinatorial regimens that optimize immunogenicity and target
tumor adaptive immunosuppressive factors.