Epcoritamab induces potent anti-tumor activity against malignant B-cells from patients with DLBCL, FL and MCL, irrespective of prior CD20 monoclonal antibody treatment

Blood Cancer J. 2021 Feb 18;11(2):38. doi: 10.1038/s41408-021-00430-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bispecific / pharmacology
  • Antigens, CD20 / immunology
  • Antineoplastic Agents, Immunological / pharmacology*
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Cell Line, Tumor
  • Humans
  • Lymphocyte Activation / drug effects
  • Lymphoma, Follicular / drug therapy*
  • Lymphoma, Follicular / immunology
  • Lymphoma, Follicular / pathology
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / immunology
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Lymphoma, Mantle-Cell / drug therapy*
  • Lymphoma, Mantle-Cell / immunology
  • Lymphoma, Mantle-Cell / pathology
  • Tumor Cells, Cultured


  • Antibodies, Bispecific
  • Antigens, CD20
  • Antineoplastic Agents, Immunological