Human regulatory T cells kill tumor cells through granzyme-dependent cytotoxicity upon retargeting with a bispecific antibody.

Journal Article (Journal Article)

A major mechanism by which human regulatory T cells (T(regs)) have been shown to suppress and kill autologous immune cells is through the granzyme-perforin pathway. However, it is unknown whether T(regs) also possess the capacity to kill tumor cells using similar mechanisms. Bispecific antibodies (bscAbs) have emerged as a promising class of therapeutics that activate T cells against tumor antigens without the need for classical MHC-restricted TCR recognition. Here, we show that a bscAb targeting the tumor-specific mutation of the epidermal growth factor receptor, EGFRvIII, redirects human CD4(+)CD25(+)FoxP3(+) T(regs) to kill glioblastoma (GBM) cells. This activity was significantly abrogated by inhibitors of the granzyme-perforin pathway. Notably, analyses of human primary GBM also displayed diffuse infiltration of granzyme-expressing FoxP3(+) T cells. Together, these data suggest that despite their known suppressive functions, tumor-infiltrating T(regs) possess potent cytotoxic mechanisms that can be co-opted for efficient tumor cell lysis.

Full Text

Duke Authors

Cited Authors

  • Choi, BD; Gedeon, PC; Herndon, JE; Archer, GE; Reap, EA; Sanchez-Perez, L; Mitchell, DA; Bigner, DD; Sampson, JH

Published Date

  • September 2013

Published In

Volume / Issue

  • 1 / 3

Start / End Page

  • 163 -

PubMed ID

  • 24570975

Pubmed Central ID

  • PMC3932050

Electronic International Standard Serial Number (EISSN)

  • 2326-6074

Digital Object Identifier (DOI)

  • 10.1158/2326-6066.CIR-13-0049


  • eng

Conference Location

  • United States