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Trispecific killer engager 161519 enhances natural killer cell function and provides anti-tumor activity against

Ying Cheng1, Xiaodong Zheng1, Xuefu Wang1

  • 1Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Institute of Immunology, University of Science and Technology of China, Hefei 230027, China.

Cancer Biology & Medicine
|December 10, 2020
PubMed
Abstract

Insights

Natural killer (NK) cells show promise for treating cold tumors. A novel trispecific killer engager (TriKE) enhanced NK cell activity and reduced tumor growth in preclinical models, offering a new cancer therapy strategy.

Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • Natural killer (NK) cells are a promising strategy for treating
  • cold tumors
  • due to their cytotoxic potential.
  • NK cell-based therapies are under active development for various cancers.

Purpose of the Study:

  • To construct and evaluate a novel trispecific killer engager (TriKE) for enhancing NK cell-mediated cancer therapy.
  • To assess the in vitro and in vivo efficacy of the TriKE in targeting CD19-positive tumors.

Main Methods:

  • A trispecific killer engager (TriKE) was engineered, incorporating anti-CD16, IL-15, and anti-CD19 components.
  • The TriKE's effect on NK cell proliferation, activation, cytokine secretion, and cytotoxicity against CD19+ targets was evaluated in vitro.
  • A preclinical B-cell lymphoma model in human peripheral blood mononuclear cell-reconstituted xenograft mice was used to assess in vivo anti-tumor efficacy.

Main Results:

  • Treatment with the 161519 TriKE significantly upregulated NK cell activation markers (CD69, CD107a) and cytokine production (IFN-γ, TNF-α).
  • The TriKE enhanced NK cell proliferation and cytotoxicity against CD19+ tumor cells.
  • In vivo studies demonstrated significant inhibition of tumor growth and prolonged overall survival in mice treated with 161519 TriKE.

Conclusions:

  • The novel 161519 TriKE effectively enhances NK cell proliferation, activation, and cytotoxicity against CD19-positive tumor cells.
  • This TriKE demonstrates significant anti-tumor activity and improves survival in a preclinical cancer model.
  • The 161519 TriKE represents a potential therapeutic agent for treating CD19-positive cancers.
Keywords:
B-cell lymphomaNK cellTrispecific antibodytrispecific killer engager (TriKE)tumor immunotherapy

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