| 主权项 |
1. A pharmaceutical composition comprising as active substance:
a) an isolated mutated human or simian lentiviral ENV protein having no or a reduced immunosuppressive activity as compared to a corresponding wild type non-mutated human or simian lentiviral ENV protein, said mutated human or simian lentiviral ENV protein resulting from mutation of the transmembrane (TM) subunit of the corresponding wild type non-mutated human or simian lentiviral ENV protein, said mutated human or simian lentiviral ENV protein comprising a mutated immunosuppressive domain (ISU) containing the following amino acid sequence:A-[I/V]-E-[K/R]-Xa-Xb-X-D-Q,(SEQ ID NO: 416) wherein, X represents any amino acid,
and either Xa is A, F, G, L or R, and Xb is any amino acid, Xa is any amino acid, and Xb is R, or Xa is A, F, G, L, R, and Xb is R, or b) at least one fragment of said isolated mutated human or simian lentiviral ENV protein having no or a reduced immunosuppressive activity as compared to the corresponding wild type non-mutated human or simian lentiviral ENV protein, said fragment comprising at least 40 amino acids, said fragment comprising a mutated immunosuppressive domain (ISU) containing the following amino acid sequence:A-[I/V]-E-[K/R]-Xa-Xb-X-D-Q,(SEQ ID NO: 416) wherein, X represents any amino acid,
and either Xa is A, F, G, L or R, and Xb is any amino acid, Xa is any amino acid, and Xb is R, or Xa is A, F, G, L, R, and Xb is R, in association with a pharmaceutically acceptable carrier, said absence or reduction of immunosuppressive activity of the above mentioned mutated human or simian lentiviral ENV protein or of the above defined fragment being liable to be assessed by the fact that in an in vivo assay involving engrafted tumor cells rejection, said tumor cells being transduced either so as to express said mutated ENV protein or said fragment (mutated ENV tumor cells), or said tumor cells being transduced so as to express the corresponding wild type non-mutated ENV protein or a fragment thereof (wild type ENV tumor cells), or said tumor cells being not transduced (normal tumor cells), the following ratio: immunosuppression index of said mutated ENV protein or of said fragment (imutated env)/immunosuppression index of wild type ENV protein (iwild type env) is less than 0.5, imutated env being defined by: (maximum area reached by mutated ENV tumor cells−maximum area reached by normal tumor cells)/(maximum area reached by normal tumor cells), and iwild type env being defined by: (maximum area reached by wild type ENV tumor cells−maximum area reached by normal tumor cells)/(maximum area reached by normal tumor cells). |
