CD16xCD33 Bispecific Killer Cell Engager (BiKE) as potential immunotherapeutic in pediatric patients with AML and biphenotypic ALL

Sarah B. Reusing, Dan A. Vallera, Angela R. Manser, Titus Vatrin, Sanil Bhatia, Martin Felices, Jeffrey S. Miller, Markus Uhrberg, Florian Babor

Research output: Contribution to journalArticlepeer-review

Abstract

Similar to pediatric acute myeloid leukemia (AML) the subgroup of biphenotypic acute lymphoblastic leukemia (ALL) is a rare complex entity with adverse outcome, characterized by the surface expression of CD33. Despite novel and promising anti-CD19 targeted immunotherapies such as chimeric antigen receptor T cells and bispecific anti-CD19/CD3 antibodies, relapse and resistance remain a major challenge in about 30% to 60% of patients. To investigate the potential role of the fully humanized bispecific antibody CD16 × CD33 (BiKE) in children with CD33+ acute leukemia, we tested whether the reagent was able to boost NK cell effector functions against CD33+ AML and biphenotypic ALL blasts. Stimulation of primary NK cells from healthy volunteers with 16 × 33 BiKE led to increased cytotoxicity, degranulation and cytokine production against CD33+ cell lines. Moreover, BiKE treatment significantly increased degranulation, IFN-γ and TNF-α production against primary ALL and AML targets. Importantly, also NK cells from leukemic patients profited from restoration of effector functions by BiKE treatment, albeit to a lesser extent than NK cells from healthy donors. In particular, those patients with low perforin and granzyme expression showed compromised cytotoxic function even in the presence of BiKE. In patients with intrinsic NK cell deficiency, combination therapy of CD16xCD33 BiKE and allogeneic NK cells might thus be a promising therapeutic approach. Taken together, CD16xCD33 BiKE successfully increased NK cell effector functions against pediatric AML and biphenotypic ALL blasts and constitutes a promising new option for supporting maintenance therapy or “bridging” consolidation chemotherapy before hematopoietic stem cell transplantation.

Original languageEnglish (US)
JournalCancer Immunology, Immunotherapy
DOIs
StateAccepted/In press - 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021, The Author(s).

Keywords

  • Antibody therapy
  • BiKE
  • Biphenotypic ALL
  • Bispecific antibodies
  • CD33
  • NK cells

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