Effects of recombinant adenovirus-mediated expression of IL-2 and IL-12 in human B lymphoma cells on co-cultured PBMCReportar como inadecuado

Effects of recombinant adenovirus-mediated expression of IL-2 and IL-12 in human B lymphoma cells on co-cultured PBMC - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Genetic Vaccines and Therapy

, 2:15

First Online: 14 October 2004Received: 28 June 2004Accepted: 14 October 2004


BackgroundModulation of the immune system by genetically modified lymphoma cell vaccines is of potential therapeutic value in the treatment of B cell lymphoma. However, the anti-tumor effect of any single immunogene transfer has so far been limited. Combination treatment of recombinant IL-2 and IL-12 has been reported to be synergistic for inducing anti-tumor responses in solid tumors but the potential of IL-2-IL-12 gene modified B cell lymphoma cells has not been explored yet.

MethodsUsing three different human B cell lymphoma cell lines and primary samples from patients with B cell neoplasms, expression levels of the coxsackie B-adenovirus receptor CAR and alpha v integrins were analyzed by fluorescence-activated cell sorter FACS. Adenoviral transduction efficiencies were determined by GFP expression analysis and IL-2 and IL-12 cytokine production was quantified by enzyme-linked immunosorbent ELISA assays. Proliferative activities of peripheral blood mononuclear cells PBMC stimulated with either cytokine derived from supernatants of transduced lymphoma cells were measured by cell proliferation MTT assays. An EuTDA cytotoxicity assay was used to compare cytotoxic activities of IL-2 and-or IL-12 stimulated PBMC against unmodified lymphoma cells.

ResultsWe found that B cell lymphoma cell lines could be transduced with much higher efficiency than primary tumor samples, which appeared to correlate with the expression of CAR. Adenoviral-expressed IL-2 and IL-12 similarly led to dose-dependent increases in proliferation rates of PBMC obtained from healthy donors. IL-2 and-or IL-12 transduced lymphoma cells were co-cultured with PBMC, which were assayed for their cytolytic activity against unmodified lymphoma cells. We found that IL-2 stimulated PBMC elicited a significant anti-tumor effect but not the combined effect of IL-2-IL-12 or IL-12 alone.

ConclusionThis study demonstrates that the generation of recombinant adenovirus modified lymphoma cell vaccines based on lymphoma cell lines expressing IL-2 and IL-12 cytokine genes is technically feasible, induces increases in proliferation rates and cytotoxic activity of co-cultured PBMC, and warrants further development for the treatment of lymphoma patients in the future.

Electronic supplementary materialThe online version of this article doi:10.1186-1479-0556-2-15 contains supplementary material, which is available to authorized users.

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Autor: Oliver Ebert - Dorothee Wilbert - Peter Buttgereit - Carsten Ziske - Dimitri Flieger - Ingo GH Schmidt-Wolf

Fuente: https://link.springer.com/

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