Cancer Immunotherapy: What we have achieved and where we are going

Immune-checkpoint inhibitors (ICIs) have revolutionized cancer care. Evidence is now emerging for the long term effects of treatment with unprecedented five-year survival in metastatic melanoma and lung cancers. Single agent anti-CTLA4 has shown prolonged effects after treatment cessation, emerging evidence similarly supports a maintained caner-directed immune-response after anti-PD1 cessation albeit with higher response rates. Various biomarkers are in use to select for ICI use.

Despite the tremendous advances achieved with ICIs, a large proportion of patients are either primary resistant or acquire resistance to ICIs. Various approaches are being employed to overcome this including combination therapy with novel ICIs as well as T cell engineering with chimeric antigen receptors (CAR) and recombinant TCRs. We are currently developing an NY-ESO1 targeting TCR for clinical use.

The brain is a common site of metastases for melanoma, lung and other tumors. Combination ICI, as opposed to single agent blockade has shown intra-cranial responses similar to extra-cranial response in melanoma. Still, the brain poses unique challenges for cancer immunotherapy. We are exploring the unique characteristics of the brain-tumor immune-response using paired intra- and extra-cranial metastases.