# US 2021/0171981 A1 · Viral vectors encoding cancer/testis antigens for use in a method of prevention or treatment of cancer > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2021/0171981 A1 - Document ID: US20210171981A1 - Status: Published application - Kind: A1 - Application number: 17/250,561 - Filed: 2019-07-30 - Published: 2021-06-10 - Earliest claimed: 2018-08-03 - Assignees: Ludwig Institute for Cancer Research - Applicants: Ludwig Institute for Cancer Research Ltd. - Inventors: Benoit J. Van Den Eynde; Carol S. Leung; Adrian S. Hill; Irina Redchenko - Web page: https://patentgrep.com/patent/US20210171981A1 ## CPC - C12N 15/86: Viral vectors - A61K 39/00118: {from embryonic or fetal origin} - A61K 39/001186: {MAGE} - A61K 39/001188: {NY-ESO} - A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines} - A61P 35/00: Antineoplastic agents - C07K 14/4748: {Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE} - C07K 14/70539: {MHC-molecules, e.g. HLA-molecules} - C07K 16/2818: {against CD28 or CD152} - C07K 16/2827: {against B7 molecules, e.g. CD80, CD86} - A61K 2039/505: {comprising antibodies} - A61K 2039/545: {characterised by the dose, timing or administration schedule} - A61K 2039/585: {wherein the target is cancer} - A61K 2039/605: {MHC molecules or ligands thereof} - C07K 2319/02: containing a signal sequence - C07K 2319/03: containing a transmembrane segment - C12N 2710/10043: viral genome or elements thereof as genetic vector - C12N 2710/10343: viral genome or elements thereof as genetic vector - C12N 2710/24043: viral genome or elements thereof as genetic vector - C12N 2710/24143: viral genome or elements thereof as genetic vector - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) ## Abstract Chimpanzee adenovirus (ChAd) and MVA virus vectors containing polynucleotide sequences encoding cancer antigens are administered sequentially to a subject in a suitable adjuvant in order to achieve a prime boost effect. The polynucleotides are expressed in situ following administration to provide a MAGEA3/linker/NY-ESO-1 fusion protein and variants thereof. Also, a hli/MAGEA3/linker/NY-ESO-1 fusion protein and variants thereof. An improved T cell response is found. In a particular synergistic therapeutic approach a triple combination of ChAdOx and MVA vectors together with chemotherapeutic agent and checkpoint inhibitor results in depleted myeloid derived suppressor cells (MDSC) and dramatically improves survival time in a mouse model of cancer. ## Claims ### Claim 1 A chimpanzee adenovirus (ChAd) vector or a modified vaccinia virus Ankara (MVA) vector encapsidating a nucleic acid molecule, the nucleic acid molecule comprising a polynucleotide sequence encoding (i) a MAGE cancer antigen and/or NY-ESO-1 cancer antigen, or immunogenic fragments thereof; or (ii) a MAGE cancer antigen and/or LAGE1 cancer antigen, or immunogenic fragments thereof, operably linked to expression control sequences which direct the translation, transcription and/or expression of the cancer antigen or fragment thereof in an animal cell, and an adenoviral packaging signal sequence. ### Claim 2 (canceled) ### Claim 3 (canceled) ### Claim 4 (canceled) ### Claim 5 (depends on 1) A ChAd or MVA vector as claimed in claim 1, wherein the MAGE antigen is MAGE 3A having an amino acid sequence of SEQ ID NO: 1 or a sequence of at least 46%; preferably at least 69%; more preferably at least 95% identity therewith; or any immunogenic fragment thereof. ### Claim 6 (depends on 1) A ChAd or MVA vector as claimed in claim 1, wherein the NY-ESO-1 cancer antigen has an amino acid sequence of SEQ ID NO: 3 or a sequence of at least 75%; preferably at least 76.7% identity therewith; or any immunogenic fragment thereof. ### Claim 7 (depends on 1) A ChAd or MVA vector as claimed in claim 1, wherein the LAGE1 cancer antigen has an amino acid sequence of SEQ ID NO: 5, or a sequence of at least 78%; preferably at least 97% identity therewith; or any immunogenic fragment thereof. ### Claim 8 (depends on 1) A ChAd or MVA vector as claimed in claim 1, wherein the polynucleotide sequence further encodes a human HLA class II histocompatibility antigen gamma chain (li) with an amino acid sequence of SEQ ID NO: 6 or a sequence of at least 79% identity therewith, or a fragment thereof, so that the cancer antigen is expressed in an animal cell as a fusion with li or fragment thereof; preferably wherein the fragment is a transmembrane domain; more preferably wherein the transmembrane domain comprises amino acid residues 30 to 55 or 30 to 61, even more preferably wherein the transmembrane domain has the amino acid sequence of SEQ ID NO: 7. ### Claim 9 (depends on 1) A ChAd or MVA vector as claimed in claim 1, wherein the polynucleotide sequence further encodes tPA with an amino acid sequence of SEQ ID NO: 8 or a sequence of at least 81% identity therewith, or a fragment thereof; so that the cancer antigen is expressed in an animal cell as a fusion with tPA or a fragment thereof; preferably wherein the fragment comprises a 21 amino acid leader sequence; more preferably the 21 amino acid leader sequence is SEQ ID NO: 9. ### Claim 10 (depends on 1) A ChAd vector as claimed in claim 1, wherein the polynucleotide sequence encodes (i) a MAGE cancer antigen or immunogenic fragment thereof and a NY-ESO-1 cancer antigen or immunogenic fragment thereof; or (ii) a MAGE cancer antigen or immunogenic fragment thereof and a LAGE1 cancer antigen or immunogenic fragment thereof, expressed in an animal cell as a fusion protein. ### Claim 11 (depends on 1) An MVA vector as claimed in claim 1, wherein the polynucleotide sequence encodes (i) a MAGE cancer antigen or immunogenic fragment thereof and/or an NY-ESO-1 cancer antigen or immunogenic fragment thereof; or (ii) a MAGE cancer antigen or immunogenic fragment thereof and/or a LAGE1 cancer antigen or immunogenic fragment thereof, expressed in an animal cell as a fusion protein, wherein at least one of the MAGE cancer antigen, NY-ESO-1 cancer antigen or LAGE1 cancer antigen is a fragment. ### Claim 12 (depends on 11) An MVA vector as claimed in claim 11, wherein the MAGE cancer antigen and NY-ESO-1 or MAGE cancer antigen and LAGE1 are immunogenic fragments. ### Claim 13 (depends on 10) A ChAd or MVA vector as claimed in claim 10, wherein the polynucleotide sequence encodes a linker of between 5 and 9 amino acids; preferably having the amino acid sequence GGGPGGG, which when expressed links the MAGE and NY-ESO-1 or LAGE1 cancer antigens or fragments thereof, in either order, as a fusion protein. ### Claim 14 (depends on 1) An immunogenic composition comprising a ChAd or MVA vector as claimed in claim 1. ### Claim 15 (depends on 14) A composition of claim 14 further comprising an adjuvant. ### Claim 16 (depends on 1) An isolated polynucleotide comprising a sequence encoding a ChAd or MVA vector of claim 1. ### Claim 17 (depends on 16) An isolated polynucleotide as claimed in claim 16, codon optimised for human codon usage. ### Claim 18 (depends on 16) A Bacterial Artificial Chromosome (BAC) clone comprising a polynucleotide of claim 16. ### Claim 19 (depends on 1) An isolated host cell comprising a ChAd and/or MVA vector as set forth in claim 1. ### Claim 20 (depends on 1) A method of preventing or treating cancer in an individual, comprising administering an effective amount of a ChAd vector and an MVA vector as set forth in claim 1, whereby the adaptive immune system of the individual is stimulated to provide an anti-cancer immune response. ### Claim 21 (depends on 20) A method of preventing or treating cancer as claimed in claim 20, wherein the administration of the ChAd and MVA vectors is carried out separately, sequentially or simultaneously. ### Claim 22 (depends on 20) A method as claimed in claim 20, further comprising administration of an effective amount of one or more checkpoint inhibitors. ### Claim 23 (depends on 22) A method as claimed in claim 22, wherein the checkpoint inhibitor is administered simultaneously, separately or concurrently with the ChAd and MVA vectors. ### Claim 24 (depends on 20) A method as claimed in claim 20, wherein the individual has received, is receiving or will receive a chemotherapy and/or radiotherapy treatment. ### Claim 25 (depends on 20) A method as claimed in any claim 20, wherein the ChAd vector is administered first. ### Claim 26 (depends on 20) A method as claimed in claim 20, wherein the ChAd and MVA vectors are administered more than once each. ### Claim 27 (depends on 20) A method as claimed in claim 20, wherein the ChAd and MVA vectors are administered in alternation. ### Claim 28 (depends on 20) A method as claimed in claim 20, wherein the period of time between each administration of a vector is in the range 5 days to 8 weeks; preferably 1 week. ### Claim 29 (depends on 22) A method as claimed in claim 22, wherein the checkpoint inhibitor blocks PD-1, CTLA-4 or PD-L1. ### Claim 30 (depends on 22) A method as claimed in claim 22, wherein the checkpoint inhibitor is selected from nivolumab, pembrolizumab, ipilimumab, tremelimumab or atezolizumab, durvaliumab or avelumab. ### Claim 31 (depends on 22) A method as claimed claim 22, wherein the cancer is non-small cell lung cancer (NSCLC), melanoma, Hodgkin lymphoma, non-Hodgkin lymphoma, urinary tract (urothelial), bladder, small cell lung cancer, renal, head & neck, sarcoma, or breast. ### Claim 32 (canceled) ### Claim 33 (canceled) ### Claim 34 (canceled) ### Claim 35 (canceled) ### Claim 36 (canceled) ### Claim 37 (canceled) ### Claim 38 (canceled) ### Claim 39 (canceled) ### Claim 40 (canceled) ### Claim 41 (canceled) ### Claim 42 (canceled) ### Claim 43 (canceled) ### Claim 44 (canceled) ### Claim 45 (canceled) ### Claim 46 (canceled) ### Claim 47 (canceled) ### Claim 48 (canceled) ### Claim 49 (depends on 1) The ChAd vector of claim 1 further comprising an adenoviral packaging signal sequence.