This year’s American Association for Cancer Research(AACR) annual meetingtook place on 1–5 April in Washington, DC, USA. The program committee Chair was Kornelia Polyak, MD, PhD, from the Dana-Farber Cancer Institute, Boston, Massachusetts.
On Monday 3 rdApril, a poster ( 1701 / 20) by Eugenio Gaudio, from the Institute of Oncology Research, Bellinzona, Switzerland, et al.titled “The novel anti-CD205 antibody drug conjugate (ADC) MEN1309 shows strong anti-tumoral activity in Diffuse Large B-Cell Lymphoma (DLBCL)” was presented.
The group exposed MEN1309 and IgG-conjugated DM4 (control) to 24 DLBCL cell lines for 72 hours. Xenografts (15 x 10 6cells/mouse, 200μL of PBS) were established subcutaneously in female NOD-SCID mice; IV treatment started when tumors reached a volume of 250–350mm 3.
- Median IC50 = 300pM; 95%CI, 200–771 with MEN1309; IgG-conjugated DM4 toxin was 100x less active = 30nM; 95%CI, 20–33
- MEN1309 caused 17/24 (71%) cell lines to undergo apoptosis
- No difference observed between DLBCL cell of origin, MYC or BCL2 translocations, or TP53 status
- MEN1309 activity highly correlated with its target expression with an inverse correlation between IC50 values and CD205 expression at flow cytometry or RT-PCR (R = -0.79, P< 0.0001)
- No correlation observed between CD205 expression and IgG-conjugated DM4 activity
- MEN1309 anti-tumor activity was
in vivoconfirmed in a DLBCL model (OCI-Ly10) characterized by high CD205 expression
- MEN1309 administered at 3 different doses: 1.25, 2.5 and 5mg/Kg every 3 weeks
- Controls treated with IgG-DM4 (5mg/Kg every 3 weeks)
- Single administration of MEN1309 at 5mg/Kg dose eradicated tumors in all mice; highly significant differences versuscontrol mice (D7, D21, D28; P< 0.01)
- MEN1309 5mg/Kg group did not undergo second treatment at D21 due to no palpable tumor present; mice remained cured 2 months later ( P< 0.0001)
- MEN1309 2.5mg/Kg delayed tumor growth versuscontrol (D21, P039)
- Reduced activity noted with MEN1309 1.25mg/Kg (D7, P012) and IgG-DM4 (D21, P0.049; D28, P0.046)
The poster concluded by stating that the novel ADC MEN1309 had strong in vitroand in vivoanti-tumor activity in DLBCL models, which is highly correlated with the expression of its target.