Use of caloric restriction mimetics for potentiating chemo-immunotherapy for the treatment of cancers

In most cases, cancer chemotherapy and immunotherapy fail to yield durable responses, and complete and permanent regression of established tumors are rare. Here the inventors show that so-called caloric restriction mimetics (CRMs), which are natural or synthetic compounds that pharmacologically mimic the effects of fasting or caloric restriction, can be used to enhance the probability of cancer cure. The administration of several chemically distinct CRMs (such as hydroxycitrate, lipoic acid and the natural polyamine spermidine) led to the complete regression and the induction of protective anticancer immune responses in mouse models. This effect was achieved when CRMs were combined with chemotherapy and immunotherapy targeting the immune checkpoint molecules CTLA-4 and/or PD-1. Hence, caloric restriction and CRMs can be used to sensitize cancers to chemo-immunotherapy.

VACCINE COMPOSITION

There is described a kit for use in inducing an immune response in a mammal, the kit includes: a first virus that expresses MAGEA3, Human Papilloma Virus E6/E7 fusion protein, human Six-Transmembrane Epithelial Antigen of the Prostate protein, or Cancer Testis Antigen 1, or a variant thereof as an antigenic protein and that is formulated to generate an immunity to the protein or variant thereof in the mammal. The kit also includes a Maraba MG1 virus encoding the same antigen, or a variant of the same antigen. The Maraba MG1 virus is formulated to induce the immune response in the mammal. The first virus is immunologically distinct from the Maraba MG1 virus. 1. A kit for use in inducing an immune response in a mammal , the kit comprising:a first virus that expresses a protein comprising an amino acid sequence of SEQ ID NO: 1, or a variant thereof, as an antigenic protein and that is formulated to generate an immunity to the protein or variant thereof in the mammal; anda Maraba MG1 virus encoding a protein comprising an amino acid sequence SEQ ID NO: 1, or a variant thereof, as an antigenic protein, the Maraba MG1 virus formulated to induce the immune response in the mammal;the first virus being immunologically distinct from the Maraba MG1 virus.2. The kit according to claim 1 , wherein the antigenic protein expressed by the first virus and the antigenic protein expressed by the Maraba MG1 virus are identical.3. The kit according to claim 1 , wherein the first virus claim 1 , the Maraba MG1 virus claim 1 , or both claim 1 , are formulated for administration as isolated viruses.4. The kit according to claim 1 , whereinthe Maraba MG1 virus includes a reverse complement and RNA version of a transgene comprising a nucleotide sequence of SEQ ID NO: 2;the first virus is a negative strand RNA virus and includes a reverse complement and RNA version of a transgene comprising a nucleotide sequence of SEQ ID NO: 2;the first virus is a DNA virus or a positive sense RNA virus and ...

VACCINE COMPOSITION

There is described a kit for use in inducing an immune response in a mammal, the kit includes: a first virus that expresses MAGEA3, Human Papilloma Virus E6/E7 fusion protein, human Six-Transmembrane Epithelial Antigen of the Prostate protein, or Cancer Testis Antigen 1, or a variant thereof as an antigenic protein and that is formulated to generate an immunity to the protein or variant thereof in the mammal. The kit also includes a Maraba MG1 virus encoding the same antigen, or a variant of the same antigen. The Maraba MG1 virus is formulated to induce the immune response in the mammal. The first virus is immunologically distinct from the Maraba MG1 virus. 1. A method of treating cancer in a mammal said cancer being a tumour expressing an HPV protein , said method comprising:a) administering a first virus comprising a nucleic acid capable of expressing a protein comprising an HPV tumour associated antigen, wherein said first virus is capable of generating immunity to said HPV tumour associated antigen;b) administering a second virus, said second virus being a Vesiculovirus, said second virus comprising a nucleic acid capable of expressing a HPV tumour associated antigen, wherein said second virus is capable of providing a therapeutic oncolytic effect in said mammal;wherein said first virus is immunologically distinct and physically; andwherein either (i) the HPV tumour associated antigen comprises an amino acid sequence that is at least 80% identical to SEQ ID NO. 7; or (ii) the second virus is Maraba MG1.2. The method of claim 1 , wherein said second virus is Maraba MG1.3. The method of claim 2 , wherein the HPV tumour associated antigen expressed by said nucleic acid in at least the first or second virus comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 7.4. The method of claim 3 , wherein the amino acid sequence is at least 90% identical to SEQ ID NO: 7.5. The method of claim 4 , wherein the amino acid sequence comprises SEQ ID NO: 7. ...

VACCINE COMPOSITION

There is described a kit for use in inducing an immune response in a mammal, the kit includes: a first virus that expresses MAGEA3, Human Papilloma Virus E6/E7 fusion protein, human Six-Transmembrane Epithelial Antigen of the Prostate protein, or Cancer Testis Antigen 1, or a variant thereof as an antigenic protein and that is formulated to generate an immunity to the protein or variant thereof in the mammal. The kit also includes a Maraba MG1 virus encoding the same antigen, or a variant of the same antigen. The Maraba MG1 virus is formulated to induce the immune response in the mammal. The first virus is immunologically distinct from the Maraba MG1 virus. 1. A heterologous prime-boost vaccine for use in the treatment of cancer in a mammal comprising:a first virus comprising a nucleic acid capable of expressing an HPV tumour associated antigen, wherein said first virus is capable of generating immunity to said HPV tumour associated antigen;a second virus, said second virus being a Vesiculovirus, said second virus comprising a nucleic acid capable of expressing a HPV tumour associated antigen, wherein said second virus is capable of providing a therapeutic oncolytic effect in said mammal;wherein said first virus is immunologically distinct and physically isolated from said second virus; andwherein either (i) the HPV tumour associated antigen comprises an amino acid sequence that is at least 80% identical to SEQ ID NO. 7; or (ii) the second virus is Maraba MG1.2. The heterologous prime-boost vaccine of claim 1 , wherein said second virus is Maraba MG1.3. The heterologous prime-boost vaccine of claim 2 , wherein the HPV tumour associated antigen expressed by said nucleic acid in at least the first or second virus comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 7.4. The heterologous prime-boost vaccine of claim 3 , wherein the amino acid sequence is at least 90% identical to SEQ ID NO: 7.5. The heterologous prime-boost vaccine of claim 4 , ...

Use of caloric restriction mimetics for potentiating chemo-immunotherapy for the treatment of cancers

In most cases, cancer chemotherapy and immunotherapy fail to yield durable responses, and complete and permanent regression of established tumors are rare. Here the inventors show that so-called caloric restriction mimetics (CRMs), which are natural or synthetic compounds that pharmacologically mimic the effects of fasting or caloric restriction, can be used to enhance the probability of cancer cure. The administration of several chemically distinct CRMs (such as hydroxycitrate, lipoic acid and the natural polyamine spermidine) led to the complete regression and the induction of protective anticancer immune responses in mouse models. This effect was achieved when CRMs were combined with chemotherapy and immunotherapy targeting the immune checkpoint molecules CTLA-4 and/or PD-l. Hence, caloric restriction and CRMs can be used to sensitize cancers to chemo-immunotherapy.

Use of caloric restriction mimetics for potentiating chemo-immunotherapy for the treatment of cancers

In most cases, cancer chemotherapy and immunotherapy fail to yield durable responses, and complete and permanent regression of established tumors are rare. Here the inventors show that so-called caloric restriction mimetics (CRMs), which are natural or synthetic compounds that pharmacologically mimic the effects of fasting or caloric restriction, can be used to enhance the probability of cancer cure. The administration of several chemically distinct CRMs (such as hydroxycitrate, lipoic acid and the natural polyamine spermidine) led to the complete regression and the induction of protective anticancer immune responses in mouse models. This effect was achieved when CRMs were combined with chemotherapy and immunotherapy targeting the immune checkpoint molecules CTLA-4 and/or PD-l. Hence, caloric restriction and CRMs can be used to sensitize cancers to chemo-immunotherapy.

Vaccine composition