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DC-based vaccine loaded with acid-eluted peptides in acute myeloid leukemia: the importance of choosing the best elution method
Authors:Stéphanie Delluc  Léa Tourneur  Didier Fradelizi  Marie-Thérèse Rubio  Carmen Marchiol-Fournigault  Gilles Chiocchia  Agnès Buzyn
Institution:Département d'Immunologie, Institut Cochin, Institut National de la Santé Et de la Recherche Médicale (INSERM) U 567, Centre National de Recherche Scientifique (CNRS) UMR 8104, Université René Descartes, Paris V, Paris, France.
Abstract:Tumor-associated peptides isolated by acid elution are frequently used for therapeutic immunization against various tumors both in mice and in humans. In acute myeloid leukemia (AML), the frequent accessibility of a large tumor burden allows for extraction of peptides from leukemia cells by using either citrate–phosphate (CP) or trifluoroacetic acid (TFA) buffer. To develop an optimal immunotherapeutic protocol for AML patients, we evaluated both in mice and in humans, the immunogenicity of peptides eluted from leukemia cells with the two acids (TFA or CP). Although ex vivo studies in mice showed that both prophylactic immunizations with mature dendritic cells (DC) loaded with TFA-peptides (DC/TFA), or CP-peptides (DC/CP), were able to stimulate specific antileukemia immune responses, only vaccination with DC/TFA was able to prevent leukemia outgrowth. Moreover, in humans, only DC/TFA generated significant antileukemia CD4+ and cytotoxic CD8+ T cell responses in vitro. In summary, these data demonstrate that the choice of the acid elution procedure to isolate immunogenic peptides strongly influences the efficacy of the antileukemia immune responses. These finding raise essential considerations for the development of immunotherapeutic protocols for cancer patients. In our model, our results argue for the use of the TFA elution method to extract immunogenic AML-associated peptides.Authors of submitted papers declare no conflict of interest or financial interest in the product or in potentially competing products held by them, their spouses and/or minor children.
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