T Cells Expressing CAR Equipped With Extracellular Domain of BTLA Are Effective Against HVEM-over-expressing Melanoma Cell Lines

Anticancer Res. 2023 Aug;43(8):3419-3427. doi: 10.21873/anticanres.16517.

Abstract

Background/aim: Several chimeric antigen receptor (CAR) T cells have been used to treat melanoma but have not shown favorable results. This study investigated whether Herpes virus entry mediator (HVEM), which is overexpressed in melanoma, is a potential novel antigen for CAR T cell therapy.

Materials and methods: A CAR construct, composed of the BTLA extracellular domain for HVEM recognition (BTLA-28z), was developed and tested.

Results: Jurkat cells transduced with BTLA-28z exhibited enhanced IL-2 secretion when incubated with HVEM-over-expressing melanoma cells. KHYG-1 cells transduced with BTLA-28z also lysed melanoma cell lines. Using primary T cells, we generated CAR T cells targeting HVEM. BTLA-28z CAR T cells exhibited excellent lytic activities against melanoma cell lines.

Conclusion: HVEM-targeting CAR T cells may be useful for the treatment of melanoma.

Keywords: BTLA; CAR T cell therapy; HVEM; immunology; melanoma; solid tumor.

MeSH terms

  • Cell Line
  • Humans
  • Immunotherapy, Adoptive*
  • Melanoma* / therapy
  • Receptors, Immunologic* / metabolism
  • Receptors, Tumor Necrosis Factor, Member 14* / genetics
  • Receptors, Tumor Necrosis Factor, Member 14* / metabolism

Substances

  • BTLA protein, human
  • Receptors, Immunologic
  • Receptors, Tumor Necrosis Factor, Member 14
  • TNFRSF14 protein, human