Restimulation of tumour-specific immunity in a patient with AML following injection with B7-1 positive autologous blasts

Leuk Res. 2003 Nov;27(11):1051-61. doi: 10.1016/s0145-2126(03)00058-4.

Abstract

Leukaemic blast cells lack co-stimulatory molecules such as B7, necessary for T-lymphocyte activation. We have used modified CD80+ (B7-1+) tumour cells, with autologous, IL-2 producing, stromal marrow cells in a series of subcutaneous vaccinations to provide a localised environment for the enhancement of cytotoxic T-lymphocytes (CTL) in a patient with acute myeloid leukaemia (AML). Localised inflammation was evident after the fifth and sixth injections with a reduction in the number of circulating blasts in the following 2 weeks. Peripheral blood in vitro CTL activity increased 36-47% after five injections.CD4 T-lymphocytes (5.7%) expanded from post-injection skin biopsies, expressed intracellular IFNgamma and perforin when exposed to autologous B7-1+ blasts and when co-cultured with either B7-1+ or unmanipulated autologous blast cells showed proliferative responses. In this patient, co-injection of B7-1+ tumour cells, together with a local source of sustained IL-2, resulted in an autologous anti-leukaemic in vitro immune response.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • B7-1 Antigen / immunology*
  • Bone Marrow Cells / immunology
  • Female
  • Humans
  • Immunization, Passive*
  • Interferon-gamma / biosynthesis
  • Leukemia, Myeloid / immunology*
  • Leukemia, Myeloid / therapy*
  • Lymphocyte Activation
  • Membrane Glycoproteins / biosynthesis
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Cytotoxic / immunology
  • Transduction, Genetic

Substances

  • B7-1 Antigen
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Perforin
  • Interferon-gamma