Primary multiple myeloma cells can be targeted efficiently by both eTCR- and CAR T cells. (A-B) Bone marrow mononuclear cells derived from 3 patients with MM were thawed and assessed by flow cytometry. MM cells were identified as CD3^–CD19^–CD45^neg/lowCD38^hiCD56^hi/low. (A) Expression of BCMA vs unstained. (B) Expression of HLA-ABC vs unstained. (C-D) Fifty thousand bone marrow mononuclear cells from HLA-B7–positive MM materials 1 and 2 were incubated with indicated T cells derived from 2 donors at designated effector-to-target ratio (E:T) ratios (5000 T cells or 50 000 T cells; for combination of BOB1-TCR T cells and BCMA-CAR T cells 2500 or 25 000 of each T-cell population were added together). (C) Representative data showing counts of viable MM cells of MM material MM1 after overnight coculture with indicated T cells derived from 1 donor in technical duplicates. Viable MM cells were identified as sytox-blue^–, CD3^–CD19^–CD45^lowCD38^hiCD56^hi/low acquired in isovolumetric flow cytometry measurements. (D) Summary of killing data on MM materials MM1 (left) and MM2 (right) subjected to recognition by T-cell products generated from 5 different donors (indicated by symbols). Statistics depict repeated measures 2-way ANOVA (paired for donors, Dunnett post hoc test). (E) Representative data showing expression of BMCA and HLA-B∗07:02 on primary MM after exposure to BCMA-CAR T cells or CMV-TCR T cells in an E:T ratio of 0.1:1. (F-G) normalized gMFIs of BCMA (AF647) (F) and HLA B7 (PE) (G) on surviving MM cells after coculture with indicated T cells in an E:T ratio of 0.1:1. The symbol shapes are analogous to those in panel E. Pooled data of both MM materials as indicated by filled or open symbols (open: MM1, closed: MM2). Statistics in panels F-G depict repeated measures 1-way ANOVA (paired for donors, Dunnett post hoc test). MM, multiple myeloma; ANOVA, analysis of variance; gMFI, geometric mean fluorescence intensity.