Abstract: The invention concerns the optimisation of the wild R9M peptide and the use of the resulting peptides for therapeutic vaccination and/or preventive vaccination against leukaemia in humans. More particularly, the invention concerns mutated immunogenic peptides derived from the human TEL/AML1 fusion protein comprising the wild R9M peptide sequence Arg-Ile-Ala-Glu-Czs-Ile-Leu-Gly-Met. The invention also concerns polynucleotides coding for the mutated R9M immunogenic peptides, cellular expression vectors comprising nucleic acid sequences expressing the mutated R9M immunogenic peptides and polyclonal or monoclonal antibodies capable of being fixed on at least one of said peptides/polynucleotides. The invention further concerns the use of said peptides, polynucleotides and/or antibodies for preparing vaccines, anti-tumoral medicines and compositions and for in vitro and in vivo stimulation of the immune response in humans.

Abstract: A recombinant vector comprising a polynucleotide containing a cis-acting central initiation region (cPPT) and a cis-acting termination region (CTS) is disclosed. These regions are of retroviral or retroviral-like origin. The vector further comprises a defined nucleotide sequence (transgene or sequence of interest) and regulatory signals for reverse transcription, expression, and packaging, wherein the regulatory signals are of retroviral or retroviral-like origin. In some embodiments the vector is incorporated into compositions for therapeutic purposes. In other embodiments the vector is incorporated into immunogenic compositions, The vector is also useful for methods such as ex vivo transfection or ex vivo transduction of non-mitotic differentiated cells.

Abstract: H-2 class I negative, HLA-A2.1 transgenic HHD mice were used for a comparative evaluation of the immunogenicity of HLA-A2.1 restricted human tumor-associated CTL epitopes and HIV 1-derived epitopes. A hierarchy was established among these epitopic peptides injected into mice in IFA which correlates globally with their capacity to bind and stabilize HLA-A2.1 molecules. A tyrosine substitution in position 1 of the HIV 1-derived epitopic peptides, which increases both their affinity for and their HLA-A2.1 molecule stabilizing capacity, was introduced in a significant proportion of them. DNA immunizations were performed using a construct comprising nucleic acids encoding the epitopes inserted into the pre-S2 segment of the hepatitis B middle glycoprotein. CTL responses against most of the inserted epitopes could be elicited simultaneously in a single animal.