Open Access

Cancer therapeutic trispecific antibodies recruiting both T and natural killer cells to cancer cells

  • Authors:
    • Kouki Kimura
    • Atsushi Kuwahara
    • Saori Suzuki
    • Takeshi Nakanishi
    • Izumi Kumagai
    • Ryutaro Asano
  • View Affiliations

  • Published online on: October 20, 2023     https://doi.org/10.3892/or.2023.8649
  • Article Number: 212
  • Copyright: © Kimura et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].

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Abstract

T cells and natural killer (NK) cells are major effector cells recruited by cancer therapeutic bispecific antibodies; however, differences in the populations of these cells in individual tumors limit the general use of these antibodies. In the present study, trispecific antibodies were created, namely T cell and NK cell engagers (TaKEs), that recruit both T cells and NK cells. Notably, three Fc‑fused TaKEs were designed, TaKE1‑Fc, TaKE2‑Fc and TaKE3‑Fc, using variable fragments targeting the epidermal growth factor receptor on tumor cells, CD3 on T cells, and CD16 on NK cells. Among them, TaKE1‑Fc was predicted to form a circular tetrabody‑like configuration and exhibited the highest production and greatest cancer growth inhibitory effects. TaKE1 was prepared from TaKE1‑Fc by digesting the Fc region for further functional evaluation. The resulting TaKE1 exhibited trispecificity via its ability to bind cancer cells, T cells and NK cells, as well as comparable or greater cancer growth inhibitory effects to those of two bispecific antibodies that recruit T cells and NK cells, respectively. A functional trispecific antibody with the potential to exert strong therapeutic effects independent of T cell and NK cell populations was developed.
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December-2023
Volume 50 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Kimura K, Kuwahara A, Suzuki S, Nakanishi T, Kumagai I and Asano R: Cancer therapeutic trispecific antibodies recruiting both T and natural killer cells to cancer cells. Oncol Rep 50: 212, 2023
APA
Kimura, K., Kuwahara, A., Suzuki, S., Nakanishi, T., Kumagai, I., & Asano, R. (2023). Cancer therapeutic trispecific antibodies recruiting both T and natural killer cells to cancer cells. Oncology Reports, 50, 212. https://doi.org/10.3892/or.2023.8649
MLA
Kimura, K., Kuwahara, A., Suzuki, S., Nakanishi, T., Kumagai, I., Asano, R."Cancer therapeutic trispecific antibodies recruiting both T and natural killer cells to cancer cells". Oncology Reports 50.6 (2023): 212.
Chicago
Kimura, K., Kuwahara, A., Suzuki, S., Nakanishi, T., Kumagai, I., Asano, R."Cancer therapeutic trispecific antibodies recruiting both T and natural killer cells to cancer cells". Oncology Reports 50, no. 6 (2023): 212. https://doi.org/10.3892/or.2023.8649