These data are consistent with limited studies with tetravalent tandem diabodies, in which cancer cell expression of CD80 or CD86 or concomitant treatment CD28 antibodies led to significantly increased activity of the bispecific antibody.28, 29 Conversely, cancer cell expression of PD-L1 or PD-L2, which are thought to act exclusively as negative regulatory ligands,18 noticeably decreased the cytotoxic activity of AMG 330. This evidence concerns the gene PDCD1LG2 and cancer.