Use of a genetically modified infectious measles virus with enhanced pro-apoptotic properties (MV-deltaC virus) in cancer therapy
The invention relates to a genetically modified infectious measles virus derived from a live-attenuated measles virus strain, in which the gene encoding the viral accessory C protein has been knocked out (MV-deltaC). It concerns in particular the use of said genetically modified infectious MV-deltaC in the treatment of malignant tumour or cancer conditions, and for the preparation of agents or compositions for such treatment.
1. A method for preparing vaccinal plasmacytoid dendritic cells (pDCs), comprising:
a. providing malignant tumor or cancer cells collected from a patient;
b. in vitro infecting the malignant tumor or cancer cells with an infectious live attenuated MV strain to yield a cell lysate, wherein the gene encoding the viral accessory C protein has been knocked out in the infectious live-attenuated MV (MV-deltaC); and
c. contacting pDCs with the cell lysate of b. to yield vaccinal pDCs.
2. The method of claim 1 , wherein the pDCs are provided by leukapheresis.
3. The method of claim 1 , wherein the malignant tumor or cancer is selected from aggressive malignant tumor, aggressive cancer, malignant mesothelioma, melanoma and lung adenocarcinoma.
4. The method of to claim 1 , wherein the live-attenuated MV strain is the Schwarz strain or the Moraten strain.
5. A method of inducing cell death of malignant cancer cells in a subject in need thereof, comprising:
(A) providing vaccinal pDCs prepared by the method of claim 1 ; and
(B) administering the pDCs to the subject.
6. The method of claim 5 , wherein the malignant cancer cells are selected from the group consisting of malignant mesothelioma cells, melanoma cells and lung adenocarcinoma cells.
7. A pharmaceutical composition for treating an aggressive malignant tumor or aggressive cancer, comprising:
(A) an infectious live-attenuated MV strain in which the gene encoding the viral accessory C protein has been knocked out (MV-deltaC); and
(B) a pharmaceutically acceptable vehicle.
8. An assembly of active ingredients for treating an aggressive malignant tumor or aggressive cancer, comprising
(i) an infectious live-attenuated MV strain in which the gene encoding the viral accessory C protein has been knocked out (MV-deltaC),
(ii) a chemotherapeutic agent, and
(iii) a pharmaceutically acceptable vehicle.
9. The assembly of active ingredients of claim 8 , further comprising vaccinal pDCs prepared by a method comprising:
a. providing malignant tumor or cancer cells collected from a patient;
b. in vitro infecting the malignant tumor or cancer cells with an infectious live attenuated MV strain to yield a cell lysate, wherein the gene encoding the viral accessory C protein has been knocked out in the infectious live-attenuated MV (MV-deltaC); and
c. contacting pDCs with the cell lysate of b. to yield vaccinal pDCs.
10. An assembly of active ingredients for treating an aggressive malignant tumor or aggressive cancer, comprising:
(i) an infectious live-attenuated MV strain in which the gene encoding the viral accessory C protein has been knocked out (MV-deltaC), and
(ii) vaccinal pDCs prepared by the method of claim 1 .