To evaluate the effects of CELMoD agents on ALNUC-mediated T cell anti-MM activity, healthy donor (HD) T cells and/or BCMA-expressing MM cell lines (H929, OPM-2, and L363) were pretreated with biologically active concentrations of POM, MEZI, IBER….ALNUC antitumor activity against the OPM-2 cell line was also enhanced by the pretreatment of T cells with MEZI and IBER, but not POM. Overall, MEZI demonstrated the greatest enhancement of ALNUC-mediated activity in this in vitro co-culture model....Priming or concurrent treatment with MEZI enhanced T cell activation, promoted T cell infiltration of tumor tissue, and increased ALNUC-induced tumor clearance in the xenograft model....The combination of ALNUC and novel CELMoD agents demonstrated enhanced T cell mediated antitumor activity both in vitro and in ex vivo MM models.