Abstract 1701: The novel anti-CD205 antibody drug conjugate (ADC) MEN1309 shows strong antitumoral activity in diffuse large B cell lymphoma (DLBCL)

Background. Up to one third of DLBCL patients still succumb to their disease: novel therapeutic approaches are needed. MEN1309 is a novel ADC consisting of an anti-CD205 monoclonal antibody conjugated to the DM4 maytansine derivative through a cleavable linker. Here, we assessed its anti-DLBCL antitumoral activity. Methods 24 DLBCL cell lines were exposed to MEN1309 and, as control, to IgG-conjugated DM4 for 72h. Cell proliferation was measured with MTT. Apoptosis activation, defined by at least 1.5 fold increase in the caspase 3/7 signal respect to controls, was measured with the Promega ApoTox-Glo Triplex Assay. Xenografts (15 x 10 6 cells/mouse, 200 μL of PBS) were established s.c. into the left flanks of female NOD-SCID mice; i.v. treatments started with tumors of 250-350 mm 3 volume. Results. MEN1309 showed strong cytotoxic activity in DLBCL (median IC50 = 300 pM; 95%CI, 200-771), while the IgG-conjugated DM4 toxin was 100x less active (30 nM; 95%CI, 20-33). MEN1309 induced apoptosis in 17/24 (71%) DLBCL. No difference was seen based upon DLBCL cell of origin, MYC or BCL2 translocations or TP53 status. MEN1309 activity was 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 Conclusions. In DLBCL models, the novel ADC MEN1309 had strong in vitro and in vivo anti-tumor activity, which is highly correlated with the expression of its target. Citation Format: Eugenio Gaudio, Chiara Tarantelli, Francesca Guidetti, Maurilio Ponzoni, Roberta Pittau Bordone, Alessio Fiascarelli, Andrea Rinaldi, Ivo Kwee, Afua Adjeiwaa Mensah, Anastasios Stathis, Davide Rossi, Georg Stussi, Emanuele Zucca, Giuseppe Merlino, Mario Bigioni, Monica Binaschi, Francesco Bertoni. The novel anti-CD205 antibody drug conjugate (ADC) MEN1309 shows strong antitumoral activity in diffuse large B cell lymphoma (DLBCL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1701. doi:10.1158/1538-7445.AM2017-1701