Fig. 3: CD56 modulation in CD38 high-expressing cells modulates ADCC response to anti-CD38 Monoclonal Antibodies.

A H929 cells infected with CD56 expression lentiviral plasmid (CD56 OE) or empty vector. On the left, western blot analysis (WB) shows CD56 expression in H929 control cells (pLV CTR) and CD56 OE cells (pLV CD56 OE); GAPDH was used as loading control. On the right, cells were assayed for their CD38 enzymatic activity (GDP-ribosyl cyclase) and intracellular NAD+ content. Data are presented as mean ± S.D (n = 3) (*p < 0.05; unpaired t test). B On the left, western blot analysis (WB) shows CD38 expression in H929 control cells (pLV CTR) and CD38 high-expression cells (pLV hCD38); GAPDH was used as loading control. On the right, surface expression level of CD56 in H929 cells overexpressing CD38 (pLV hCD38) transduced with CD56 knockdown (CD56 pLV shRNA#2) or scramble control (pLV SCR). C ADCC assays were conducted using H929 CD38OE cells transduced with scramble control (pLV SCR) or shRNA targeting CD56 (pLV CD56 shRNA#2). Effector-to-Target (E:T) ratios were evaluated using NK cells from healthy donors, with treatment conditions including Daratumumab (DARA, 10 µg/mL) and Isatuximab (ISA, 10 µg/mL). D Progression-free survival (PFS) from the first day of Isa-based therapies (11 Isa-PD and 9 Isa-KD) in our cohort of RRMM patients exhibiting high (red) or low (blue) levels of CD56 on their bone marrow plasma cells. Log rank test; p = 0.046.