High-throughput screening to identify enhancers of anti-MM immune cytotoxicity. Luc⁺ MM.1S cells were plated in the presence or absence of prestimulated PBMCs (IL-2 for 24 hours) in 96-well plates. Compounds from an NCI-derived chemical library were then added with the use of a pin transfer system (1μM final concentration) to plates with continued IL-2 stimulation (10 ng/mL) during coculture. After culture for 4 hours, we evaluated each drug's ability to enhance antitumor cytotoxicity compared with the absence of drug (A; red). As a counter screen, we evaluated each drug's direct antitumor activity (A; black) and ranked in descending order of direct anti-MM activity (n = 4 for each condition). One drug, didemnin B, which showed enhanced activity in the presence versus absence of PBMCs in the high-throughput screen (A), was further evaluated for its immunostimulatory activity. Luc⁺ MM.1S were cultured for 4 hours at increasing PBMC-to-tumor cell ratios in the presence and absence of 250nM didemnin B, and enhanced immune myeloma cytotoxicity was detected in the presence of drug (B).