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G Buffenoir

Publications and source records attributed to G Buffenoir.

5 recordsLinked to original sources
PubMed2002

Gene transfer of CD154 and IL12 cDNA induces an anti-leukemic immunity in a murine model of acute leukemia.

IL12 is an essential cytokine for the generation of T helper 1 response, natural killer (NK) cells and cytotoxic T lymphocyte (CTL) stimulation. CD154 triggers CD40 on antigen-presenting cells, thus inducing antigen presentation to the immune system and production of IL12. As IL12 and CD154 share several pathways mediating immune response, we investigated in an aggressive murine model of acute leukemia the relative antileukemic efficiency of IL12, CD154 and IL12 + CD154 gene transfer. Live leukemic cells transduced by IL12, CD154, and IL12 + CD154 showed reduced leukemogenicity but CD154 protective effect was reduced when 10(6) leukemic cells were injected. Vaccines with lethally irradiated IL12-transduced cells were able to cure mice previously injected with 10(4) leukemic cells and adoptive transfer of IL12-induced antileukemic immunity protected recipient mice. NK cytotoxicity was enhanced in mice vaccinated with leukemic cells transduced by IL12, CD154, and CD154 + IL12. IL12 transduced cells induced IFN-gamma mRNA in CD4(+) and CD8(+) T cells isolated from the spleen of vaccinated animals, however, in vivo depletion experiments showed that IL12 vaccine effect was CD4(+) but not CD8(+) T cell dependent. We conclude that IL12 gene is a more potent candidate than CD154 for gene therapy of acute leukemia.

Acute Disease↗
PubMed2000

Gene transfer of GM-CSF, CD80 and CD154 cDNA enhances survival in a murine model of acute leukemia with persistence of a minimal residual disease.

Gene transfer of various cytokines and co-stimulatory molecules has been reported to induce a potent antileukemic immunity in murine models, however, the relative efficiency and possible synergistic effects between candidate genes have not been extensively investigated. We analyzed in a murine model of BCR/ABL acute leukemia whether gene transfer of CD154, CD80 or GM-CSF as a single agent or combination of CD154 + GM-CSF, CD80 + CD154 and GM-CSF + CD80 in leukemic cells could enhance survival. We observed that CD154 gene transfer induced a marked inhibition of leukemogenicity, and also that CD154 and combination of GM-CSF and CD80 gene transfer protected mice against subsequent challenge with leukemic cells and had a therapeutic effect for a pre-established leukemia disease. We also found minimal residual leukemic disease by RT-PCR for 6 to 12 months in 0 to 25% of animals injected with transduced leukemic cells and surviving the challenge without evidence of disease, except in the control empty plasmid group where very few mice survived the challenge but all of those were positive by RT-PCR. These findings suggest that leukemic cell vaccination by gene transfer can induce a tumor dormancy phenomenon compatible with long-term survival.

Acute Disease↗
PubMed2000

gamma-ray irradiation induces B7.1 expression in myeloid leukaemic cells.

Expression of B7 molecules provides co-stimulatory signals to T lymphocytes, which prevent the induction of anergy. It has been previously reported that B7.1 gene transfer in a murine leukaemia model induced a potent antileukaemic immunity and that relative expression of B7.1 and B7.2 in human acute myeloid leukaemia (AML) had prognostic significance. As ex vivo engineering of leukaemic cells for immunotherapy protocols would require prior irradiation of these cells before reinjection to the patient, we investigated in murine and leukaemic cell lines and in 20 ex vivo primary cultured acute myeloid leukaemic cells the effect of gamma-irradiation on the expression of B7 molecules. We observed that gamma-irradiation enhanced B7.1 molecule expression in murine leukaemic cell lines and in B7.2 molecules in human HL60 and K562 cell lines. gamma-Irradiation induced B7.1 molecule expression in 90% AML samples but only 21% showed B7.2 molecule expression enhancement. B7.1 expression was increased both at the protein and RNA level in human AML cells but only at the protein level in the DA1-3b murine cell line. Oxidative stress increased B7.1 expression in the murine DA1-3b cell line but human cell lines and AML samples remained unaffected both by heat shock and oxidative stress, suggesting different pathways of B7.1 induction between mouse and human cells. Our data show that B7.1 expression can be induced by ex vivo irradiation of AML cells, indicating that these cells can express co-stimulatory molecules without gene transfer.

Animals↗
PubMed1997

[Clinical value of the estimation of growth kinetics of primary ovarian cancer recurrences by CA125 doubling time].

The aim of this retrospective work was to study the clinical importance of growth rate determination for ovarian cancer primary recurrence in term of CA125 doubling time (dt). Fifty-one patients with epithelial ovarian carcinoma stage III or IV who developed a recurrence were included. Eighteen spontaneous dt values were calculated in non-treated patients during follow-up and 33 apparent dt values were estimated in patients undergoing treatment during CA125 increase before the clinical and/or radiological diagnosis of recurrence. No early treatment of the recurrence has permitted a drop in CA125 level. We applied exponential regression models to CA125 individual kinetics in order to calculate dt values. Individual dt values vary from 5 to 375 days. Spontaneous and apparent dt medianes (respectively 64 and 39 days) are not significantly different. Among all early clinical, histological, biological and therapeutic parameters, the initial CA125 half-life calculated during the third courses of the first-line chemotherapy is the unique predictive parameter of dt (relative risk (RR) = 78; p < 0.01). The prognostic impact was more important in spontaneous dt values than in apparent ones. Being spontaneous or apparent dt was the major predictive parameter of the delay between the initial CA125 increase and clinical and/or radiological signs of recurrence (RR = 0.3; p < 0.0001). Its prognostic impact is superior to the T1/2 one (RR = 2.9; p = 0.0010). For equivalent treatments, dt (RR = 0.4; p < 0.0001) and T1/2 (RR = 4.0; p < 0.0001) are the only predictive parameters of the survival after CA125 increase. This work shows that dt was an essential predictive parameter of ovarian epithelial tumor recurrences.

Aged↗