CTLA4 and melanoma: To circumvent the systemic side effects of those therapies, anti-PD-L1 and CTLA4 antibodies were conjugated to the extracellular matrix protein-PIGF-2 (placenta growth factor 2) to provide a local treatment in animal models of melanoma; this resulted in enhanced efficacy with reduction of tumor growth and improved survival (Ishihara et al., 2017).