Novel Immunotherapy Combinations

Abstract

Purpose of review: The last decade witnessed an explosion in immunotherapeutic agent approvals for various malignancies. The success of immune checkpoint inhibitors (CTLA-4 and PD-1/PD-L1) in melanoma quickly sprung to other cancer types and are considered the emerging face of oncology.

Recent findings: Antibodies to CTLA-4 were first to enter the field, quickly followed by PD-1/PD-L1 inhibitors. Combination anti-CTLA4 and anti-PD-1/PD-L1 therapies were investigated, and after demonstrating improved responses, rapidly gained approval. Certain tumor types previously considered non-immunogenic also demonstrated durable responses which has been a remarkable discovery. However, not all tumor types respond to immunotherapies and it is widely recognized that tumor-specific immune inflammatory status predicts the best responders. Ongoing translational work indicates specific upregulation in additional immune checkpoints that circumvent response to anti-CTLA4 and anti-PD-1/PD-L1 antibodies. Here, we provide a comprehensive review of promising therapies on the horizon with unique combinations designed to overcome resistance or expand the pool of treatment responders.

Keywords: CTLA-4; Immune checkpoint inhibitors; Immunotherapy combinations; Melanoma; PD-1; Tumor microenvironment.