Attenuated Strains of Oncolytic Rhabdovirus and Uses Thereof in Tumor Treatment

An isolated peptide encoded by an amino acid sequence, wherein the amino acid sequence comprises a sequence which is at least 80%, preferably at least 90%, more preferably at least 95% and most preferably at least 98% identical to an amino acid sequence of SEQ ID NO:

• 1, and the amino acid sequence has amino acid substitutions at position 21, position 51, position 111 and position 221 as compared with SEQ ID NO:
• 1;
• preferably, the amino acid sequence encoding the isolated peptide has the following mutations:
• (i) mutation of glycine G to glutamic acid E at position 21,
• (ii) mutation of methionine M to alanine A at position 51,
• (iii) mutation of leucine L to phenylalanine F at position 111, and
• (iv) mutation of valine V to phenylalanine F at position 221;
• more preferably, the amino acid sequence is a sequence as set forth in SEQ ID NO:3.

A method for slowly and continuously killing abnormally proliferating cells, comprising a step of contacting the abnormally proliferating cells with a) recombinant oncolytic rhabdovirus that generates a modified matrix protein (M), wherein an amino acid sequence of the modified matrix protein (M) comprises a sequence which is at least 80%, preferably at least 90%, more preferably at least 95% and most preferably at least 98% identical to an amino acid sequence as set forth in SEQ ID NO:

• 1;
• b) a composition comprising an isolated recombinant oncolytic rhabdovirus that comprises a nucleic acid fragment that encodes for said modified matrix protein (M), optionally wherein said isolated recombinant oncolytic rhabdovirus is attenuated;
• and
• c) a vaccine comprising (1) a therapeutically effective amount of one or more said recombinant oncolytic rhabdoviruses comprising said modified matrix protein (M);
• (2) a second oncolytic agent;
• or 3) a second antitumor preparation;
• optionally, wherein the method further comprises i) administering a second oncolytic virus selected from the group consisting of rhabdovirus, vaccinia virus herpes virus measles virus Newcastle disease virus adenovirus, alphavirus, parvovirus, enterovirus strain attenuated oncolytic virus and attenuated rhabdovirus;
• or ii) administering a second antitumor preparation selected from the group consisting of immunotherapeutic agent, chemotherapeutic agent, radiotherapeutic agent, small molecule, macromolecule, cell, viral vector, gene vector, DNA, RNA, polypeptide and nanocomposite.

A method for inducing immune response in a subject, wherein the method comprises administering to a subject one or more selected from the group consisting of

• a) a recombinant oncolytic rhabdovirus that generates a modified matrix protein (M), wherein an amino acid sequence of the modified matrix protein (M) comprises a sequence which is at least 80%, preferably at least 90%, more preferably at least 95% and most preferably at least 98% identical to an amino acid sequence as set forth in SEQ ID NO:
• 1;
• b) a composition comprising an isolated recombinant oncolytic rhabdovirus that comprises a nucleic acid fragment that encodes for said modified matrix protein (M), optionally wherein said isolated recombinant oncolytic rhabdovirus is attenuated;
• and
• c) a vaccine comprising (1) a therapeutically effective amount of one or more said recombinant oncolytic rhabdoviruses comprising said modified matrix protein (M);
• (2) a second oncolytic agent;
• or 3) a second antitumor preparation;
• optionally, wherein the method further comprises i) administering a second oncolytic virus selected from the group consisting of rhabdovirus, vaccinia virus, herpes virus, measles virus, Newcastle disease virus, adenovirus, alphavirus, parvovirus, enterovirus strain, attenuated oncolytic virus, and attenuated rhabdovirus;
• or ii) administering a second antitumor preparation selected from the group consisting of immunotherapeutic agent, chemotherapeutic agent, radiotherapeutic agent, small molecule, macromolecule, cell, viral vector, gene vector, DNA, RNA, polypeptide and nanocomposite.

A method for inducing and promoting antitumor immune response or eliminating immunosuppression in a microenvironment of a tumor tissue, comprising a step of contacting a tumor or a tumor tissue with a) recombinant oncolytic rhabdovirus that generates a modified matrix protein (M), wherein an amino acid sequence of the modified matrix protein (M) comprises a sequence which is at least 80%, preferably at least 90%, more preferably at least 95% and most preferably at least 98% identical to an amino acid sequence as set forth in SEQ ID NO:

• 1;
• b) a composition comprising an isolated recombinant oncolytic rhabdovirus that comprises a nucleic acid fragment that encodes for said modified matrix protein (M), optionally wherein said isolated recombinant oncolytic rhabdovirus is attenuated;
• and
• c) a vaccine comprising (1) a therapeutically effective amount of one or more said recombinant oncolytic rhabdoviruses comprising said modified matrix protein (M);
• (2) a second oncolytic agent;
• or 3) a second antitumor preparation;
• optionally, wherein the method further comprises i) administering a second oncolytic virus selected from the group consisting of rhabdovirus, vaccinia virus, herpes virus, measles virus, Newcastle disease virus, adenovirus, alphavirus, parvovirus, enterovirus strain, attenuated oncolytic virus, and attenuated rhabdovirus;
• or ii) administering a second antitumor preparation selected from the group consisting of immunotherapeutic agent, chemotherapeutic agent, radiotherapeutic agent, small molecule, macromolecule, cell, viral vector, gene vector, DNA, RNA, polypeptide and nanocomposite.