DLBCL

AACR 2017 poster 1701/20 – MEN1309, a novel anti-CD205 antibody drug conjugate, shows strong anti-tumor activity in Diffuse Large B-Cell Lymphoma

This year’s American Association for Cancer Research (AACR) annual meeting took 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 3rd April, 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 106 cells/mouse, 200μL of PBS) were established subcutaneously in female NOD-SCID mice; IV treatment started when tumors reached a volume of 250–350mm3.

Key Highlights:
  • 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 vivo confirmed 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 versus control 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 versus control (D21, P039)
    • Reduced activity noted with MEN1309 1.25mg/Kg (D7, P012) and IgG-DM4 (D21, P 0.049; D28, P 0.046)

The poster concluded by stating that the novel ADC MEN1309 had strong in vitro and in vivo anti-tumor activity in DLBCL models, which is highly correlated with the expression of its target.

Reference:
  1. Gaudio E. et al. The novel anti-CD205 antibody drug conjugate (ADC) MEN1309 shows strong antitumoral activity in diffuse large B cell lymphoma (DLBCL) [Poster]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; 2017. Poster nr [1701 / 20].