naratuximab emtansine (DEBIO 1562)

Anti-IL6 antibody tocilizumab improved the ADC's cytotoxic activity in CD37+ cells...Adding idelalisib or venetoclax overcame resistance in the resistant derivative and improved the cytotoxic activity in the parental cells. In conclusion, targeting B-cell lymphoma with the naratuximab emtansine showed vigorous anti-tumor activity as a single agent, which was also observed in models bearing genetic lesions associated with inferior outcomes, such as MYC translocations and TP53 inactivation or R-CHOP resistance. Resistant DLBCL models identified active combinations of naratuximab emtansine with drugs targeting IL6, PI3Kδ, and BCL2.

Our work revealed that the clinically relevant anti-CD37 antibody drug conjugate (ADC) Debio 1562 (αCD37-DM1) is highly cytotoxic to AML blasts, but not normal hematopoietic stem cells. We found that αCD37-DM1 improved clinical outcomes and overall survival in multiple in vivo models of AML. Together, these data demonstrate that targeting CD37 with an ADC such as αCD37-DM1 is a feasible and promising therapeutic option for the treatment of AML.

DL analysis of the co-expression and spatial arrangement of CD37 and CD20 positive cells in pre-treatment biopsies of DLBCL patients could potentially be used as a predictive biomarker for a response to a combination treatment of naratuximab emtansine and rituximab in DLBCL, and may improve patient stratification for further clinical trials.

DL analysis of the co-expression and spatial arrangement of CD37 and CD20 in pre-treatment biopsies of DLBCL patients could potentially be used as a predictive biomarker for a response to a combination treatment of anti-CD37 and anti-CD20 drugs in DLBCL, and may improve patient stratification for further clinical trials.