Challenges and Unmet Needs

To maximize benefit and minimize risk, it is critical to know whether a particular checkpoint inhibitor is effective in augmenting the anti-tumor immune response in a given patient.

To determine whether a checkpoint inhibitor may be effective, immune staining is used to determine whether its target is expressed by the tumor. To determine whether a tumor is antigenic and may therefore elicit an immune response, tumor DNA sequencing is used to identify novel antigens or neoantigens, which are absent in normal tissues.

These methods characterize the tumor phenotype, and are not foolproof. Several checkpoints act simultaneously to modulate anti-tumor immune responses. For this reason, the dominant checkpoint by which a tumor escapes immune attack may not be targeted by a particular inhibitor. Further, whether the immune system ‘sees’ the tumor as antigenic, and whether the anti-tumor response is enhanced by a checkpoint inhibitor cannot be determined by phenotypic characterization.