Patent classifications
C12N2710/24171
HLA-A24 agonist epitopes of MUC1-C oncoprotein and compositions and methods of use
The invention provides a human cytotoxic T lymphocyte (CTL) agonist epitope from the C-terminal subunit of mucin 1 (MUC1-C), which can be used as a peptide, polypeptide (protein), and/or in vaccine or other composition for the prevention or therapy of cancer. The invention further provides a nucleic acid encoding the peptide, protein, or polypeptide, a vector comprising the nucleic acid, a cell comprising the peptide, polypeptide, nucleic acid, or vector, and compositions thereof.
Oncolytic Immunotherapy by Tumor Micro-Environment Remodeling
The disclosure relates to modified oncolytic viruses. The modified oncolytic viruses of the disclosure comprise modification in the viral genome encoding exogenous nucleic acids to enhance the oncolytic immunotherapy by remodeling the tumor microenvironment and with enhanced systemic delivery. The disclosure further relates to compositions comprising the modified oncolytic viruses, kits containing the same, and methods of using the oncolytic viruses.
Immune modulation
The present invention relates to a poxvirus vector comprising a nucleic acid sequence encoding a fusion protein comprising: (i) a peanut allergen selected from list consisting of at least two peanut allergens from ara h 1, ara h 2, ara h 3, ara h 4, ara h 5, ara h 6. ara h 7, ara h 8, ara h 9, ara h I O and ara h I I or a derivative or part thereof having at least 70% sequence identity thereto, and (ii) a profeasome degradation tag to enhance intracellular degradation of the fusion protein. Methods of desensitizing or inducing tolerance to a peanut allergen and/or suppressing an allergic response to a peanut allergen are also disclosed.
SYNTHETIC MODIFIED VACCINIA ANKARA (SMVA) BASED CORONAVIRUS VACCINES
Disclosed are synthetic modified vaccinia ankara (MVA)-based vaccines for preventing or treating coronavirus infections and methods of producing the vaccines. Specifically, the disclosure provides a vaccine composition comprising: (i) a single synthetic DNA fragment or two or more synthetic DNA fragments comprising the entire genome of an MVA, and (ii) one or more DNA sequences encoding one or more coronavirus antigens, subunits, or fragments thereof, inserted in one or more insertion sites of the MVA for preventing or treating coronavirus infections.
HLA-A24 AGONIST EPITOPES OF MUC1-C ONCOPROTEIN AND COMPOSITIONS AND METHODS OF USE
The invention provides a human cytotoxic T lymphocyte (CTL) agonist epitope from the C-terminal subunit of mucin 1 (MUC1-C), which can be used as a peptide, polypeptide (protein), and/or in vaccine or other composition for the prevention or therapy of cancer. The invention further provides a nucleic acid encoding the peptide, protein, or polypeptide, a vector comprising the nucleic acid, a cell comprising the peptide, polypeptide, nucleic acid, or vector, and compositions thereof.
DELIVERY OF SIALIDASE TO CANCER CELLS, IMMUNE CELLS AND THE TUMOR MICROENVIRONMENT
The present application provides methods and compositions for treating cancers (such as solid tumors) using a recombinant oncolytic virus encoding a sialidase. In some embodiments, the oncolytic virus further encodes one or more other heterologous proteins. In some embodiments, the recombinant oncolytic virus is delivered via an engineered immune cell. In some embodiments, the present application provides methods and compositions for treating cancers using a recombinant oncolytic vims encoding a sialidase or another heterologous protein and an engineered immune cell (e.g., a CAR-T, CAR-NK, or CAR-NKT cell) expressing a chimeric receptor capable of binding to the sialidase or other heterologous protein.
Immuno-Oncolytic Therapies
The present invention relates to oncolytic vaccinia viruses which have been modified to promote anti-tumor immunity and/or reduce host immunity and/or antibody response against the virus. It is based, at least in part, on the discovery that oncolytic vaccinia virus (i) bearing a genome deletion of a gene that reduces T cell immunity (interleukin-18 binding protein); (ii) treated with a sialidase enzyme which is believed to reduce TLR2 activation and therefore the antibody response; (iii) carrying a gene that enhances cytotoxic T lymphocyte induction (e.g., TRIF) and/or (iv) reduces tumor myeloid-derived suppressor cells by reducing prostaglandin E2 reduces tumor growth. Accordingly, the present invention provides for immunooncolytic vaccinia viruses and methods of using them in the treatment of cancers.
GENETICALLY ENGINEERED ONCOLYTIC VACCINIA VIRUSES AND METHODS OF USES THEREOF
The present invention provides pharmaceutical compositions comprising an oncolytic vaccinia virus and methods of using such pharmaceutical compositions for treating a subject having a cancer.
ONCOLYTIC VACCINIA VIRUS
Provided is an oncolytic virus having both improved safety and productivity. Provided are: a conditionally replicating vaccinia virus which lacks the functions of a vaccinia virus growth factor (VGF), an extracellular signal-regulated kinase (ERK) activation protein, and a ribonucleotide reductase (RNR), is not replicated in a normal cell, is selectively replicable in a proliferative cell, and has improved safety; and a conditionally replicating vaccinia virus which lacks the functions of a VGF, an ERK activation protein, and an RNR, is not replicated in a normal cell, is selectively replicable in a proliferative cell, and has improved safety and productivity, and in which a gene encoding an extracellular enveloped virus (EEV)-related protein is substituted with a gene corresponding to another vaccinia virus strain having a high EEV-producing ability.
USE OF MVA OR MVADELTAE3L AS IMMUNOTHERAPEUTIC AGENTS AGAINST SOLID TUMORS
The present disclosure relates to modified vaccinia Ankara (MVA) virus or MVAΔE3L delivered intratumorally or systemically as an anticancer immunotherapeutic agent, alone, or in combination with one or more immune checkpoint blocking agents for the treatment of malignant solid tumors. Particular embodiments relate to mobilizing the host's immune system to mount an immune response against the tumor.