Ex Vivo Study Identifies Determinants of Response to Bispecific Antibodies

An ex vivo study has identified a distinct regulatory T-cell phenotype that may contribute to the failure of bispecific antibody (BsAb) treatment and suggests drug combinations that might improve these agents’ efficacy. The study, by a team at the University of Heidelberg in Germany, appeared in the journal Blood Advances in December.

The authors state that to their knowledge the study is the first to investigate the ex vivo response to BsAbs using primary lymph node–derived lymphocytes from patients with nodal B-cell non-Hodgkin lymphoma and note that clinical studies are needed to confirm their findings.

Senior author Sascha Dietrich and colleagues demonstrated that response to BsAbs was significantly associated with T-cell expansion and secretion of effector molecules but not with expression of T-cell exhaustion, activation markers, or formation of intercellular contacts. Additionally, high expression of Helios and low expression of ICOS were associated with BsAb failure. This “distinct regulatory T-cell phenotype,” the authors write, “might be an essential factor for failure of BsAb treatment.”

The addition of lenolidomide “significantly enhanced” the B-cell killing activity of CD19-BsAb, T-cell expansion, and the secretion of effector molecules. Lenalidomide also enhanced the activity of CD20-BsAb. Similar but less-pronounced effects were seen with combinations of the checkpoint inhibitors atezolizumab or nivolumab with CD19-BsAb or CD20-BsAb.

  • Roider T, Brinkmann BJ, Kim V, et al. An autologous culture model of nodal B-cell lymphoma identifies ex vivo determinants of response to bispecific antibodies. Blood Adv. 2021;5(23):5060-5071. doi:10.1182/bloodadvances.2021005400

Tags: study, transplantation, Cellular therapy, BiTEs, Transplant, cell therapy, antibodies, determinants, bispecific, ex vivo

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