Completely mismatched allogeneic CD3/CD28 cross-linked Th1 memory cells elicit anti-leukemia effects in unconditioned hosts without GVHD toxicity

Leuk Res. 2008 Dec;32(12):1903-13. doi: 10.1016/j.leukres.2008.05.007. Epub 2008 Jun 18.


Fully allogeneic CD3/CD28 cross-linked Th1 cells were found to elicit host-mediated anti-leukemia effects without GVHD toxicity. Mice inoculated with a lethal dose of BCL1 leukemia demonstrated significantly enhanced survival after allogeneic Th1 treatment. Cure rates of 12.5% with a single allogeneic cell infusion and 31.25% with multiple infusions were demonstrated. Cured mice were able to reject rechallenge with a lethal dose of tumor without further treatment. These results suggest that use of intentionally mis-matched, Th1 memory cells infused with cross-linked CD3/CD28 could represent a novel clinical approach to eliciting potent anti-tumor effects in patients without conditioning and without GVHD toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Transplantation / adverse effects
  • CD28 Antigens / immunology
  • CD3 Complex / immunology
  • Cross-Linking Reagents / pharmacology
  • Disease Models, Animal
  • Female
  • Graft vs Host Disease / prevention & control*
  • Graft vs Leukemia Effect / immunology*
  • Histocompatibility Testing
  • Humans
  • Immunologic Memory*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / therapy
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Survival Analysis
  • Th1 Cells / drug effects
  • Th1 Cells / transplantation*
  • Transplantation, Homologous


  • CD28 Antigens
  • CD3 Complex
  • Cross-Linking Reagents