| Autor: |
van der Horst HJ; Department of Hematology, Cancer Center Amsterdam, Amsterdam University Medical Center, Location VUMC, Amsterdam, Netherlands., de Jonge AV; Department of Hematology, Cancer Center Amsterdam, Amsterdam University Medical Center, Location VUMC, Amsterdam, Netherlands., Hiemstra IH; Genmab, Utrecht, Netherlands., Gelderloos AT; Department of Hematology, Cancer Center Amsterdam, Amsterdam University Medical Center, Location VUMC, Amsterdam, Netherlands., Berry DRAI; Department of Pathology, Amsterdam University Medical Center, Location VUMC, Amsterdam, Netherlands., Hijmering NJ; Department of Pathology, Amsterdam University Medical Center, Location VUMC, Amsterdam, Netherlands., van Essen HF; Department of Pathology, Amsterdam University Medical Center, Location VUMC, Amsterdam, Netherlands., de Jong D; Department of Pathology, Amsterdam University Medical Center, Location VUMC, Amsterdam, Netherlands., Chamuleau MED; Department of Hematology, Cancer Center Amsterdam, Amsterdam University Medical Center, Location VUMC, Amsterdam, Netherlands., Zweegman S; Department of Hematology, Cancer Center Amsterdam, Amsterdam University Medical Center, Location VUMC, Amsterdam, Netherlands., Breij ECW; Genmab, Utrecht, Netherlands., Roemer MGM; Department of Pathology, Amsterdam University Medical Center, Location VUMC, Amsterdam, Netherlands., Mutis T; Department of Hematology, Cancer Center Amsterdam, Amsterdam University Medical Center, Location VUMC, Amsterdam, Netherlands. t.mutis@amsterdamumc.nl. |
| Abstrakt: |
Epcoritamab (DuoBody-CD3xCD20, GEN3013) is a novel bispecific IgG1 antibody redirecting T-cells toward CD20 + tumor cells. Here, we assessed the preclinical efficacy of epcoritamab against primary tumor cells present in the lymph node biopsies from newly diagnosed (ND) and relapsed/refractory (RR) B-NHL patients. In the presence of T-cells from a healthy donor, epcoritamab demonstrated potent activity against primary tumor cells, irrespective of prior treatments, including CD20 mAbs. Median lysis of 65, 74, and 84% were achieved in diffuse large B-cell lymphoma (n = 16), follicular lymphoma (n = 15), and mantle cell lymphoma (n = 8), respectively. Furthermore, in this allogeneic setting, we discovered that the capacity of B-cell tumors to activate T-cells was heterogeneous and showed an inverse association with their surface expression levels of the immune checkpoint molecule Herpesvirus Entry Mediator (HVEM). In the autologous setting, when lymph node (LN)-residing T-cells were the only source of effector cells, the epcoritamab-dependent cytotoxicity strongly correlated with local effector cell-to-target cell ratios. Further analyses revealed that LN-residing-derived or peripheral blood-derived T-cells of B-NHL patients, as well as heathy donor T-cells equally mediated epcoritamab-dependent cytotoxicity. These results show the promise of epcoritamab for treatment of newly-diagnosed or relapsed/refractory B-NHL patients, including those who became refractory to previous CD20-directed therapies. |
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