Restimulation of tumour-specific immunity in a patient with AML following injection with B7-1 positive autologous blasts.
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.
Hicks
Christine
C
Department of Haematology, Prince of Wales Hospital, Randwick, Sydney, NSW 2031, Australia. c.hicks@student.unsw.edu.au
Cheung
Carol
C
Lindeman
Robert
R
D000368:Aged; D018122:B7-1 Antigen / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D007371:Interferon-gamma / Q000096:biosynthesis; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000628:therapy*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014161:Transduction, Genetic
D018122:B7-1 Antigen; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D007371:Interferon-gamma