Hematopoietic lineage-converted T cells carrying tumor-associated antigen-recognizing TCRs effectively kill tumor cells

J Immunother Cancer. 2020 Jul;8(2):e000498. doi: 10.1136/jitc-2019-000498.

Abstract

Tumor-associated antigen (TAA) T-cell receptor (TCR) gene-engineered T cells exhibit great potential in antitumor immunotherapy. Considering the high costs and low availability of patient-derived peripheral blood T cells, substantial efforts have been made to explore alternatives to natural T cells. We previously reported that enforced expression of Hoxb5 converted B cells into induced T (iT) cells in vivo Here, we successfully regenerated naive OT1 (major histocompatibility complex I restricted ovalbumin antigen) iT cells (OT1-iT) in vivo by expressing Hoxb5 in pro-pre-B cells in the OT1 transgenic mouse. The OT1-iT cells can be activated and expanded in vitro in the presence of tumor cells. Particularly, these regenerated OT1-iT cells effectively eradicated tumor cells expressing the TAA (ovalbumin) both in vitro and in vivo This study provides insights into the translational applications of blood lineage-transdifferentiated T cells in immunotherapy.

Keywords: T lymphocytes; immunotherapy; melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / metabolism*
  • Humans
  • Immunotherapy / methods*
  • Mice
  • Receptors, Antigen, T-Cell / immunology*

Substances

  • Antigens, Neoplasm
  • Receptors, Antigen, T-Cell