Polypeptide-nucleic acid conjugate for immunoprophylaxis or immunotherapy for neoplastic or infectious disorders
First Claim
1. An isolated antibody-nucleic acid or peptide-nucleic acid conjugate comprising:
- i) an antibody or peptide that specifically binds to a cellular component of;
a) a tumor cell;
b) tumor vasculature; and
/or c) a component of a tumor microenvironment; and
ii) one or more immunostimulatory nucleic acid sequences (INAS), wherein one or more of the nucleic acid sequences comprise a pathogen-associated molecular pattern (PAMP).
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Abstract
The present invention discloses compositions which induce cross-activation of immune mediated and direct death signaling in targeted cells by exploiting the properties of a antibody/peptide-nucleic acid conjugate. The conjugate is able to simultaneously activate multiple death signaling mechanisms that are specifically targeted to neoplastic cells, including tumor cells. Methods of using the conjugate of the present invention as an immunotherapeutic modality for the treatment or prevention of neoplastic diseases or other disorders is also disclosed. Further, methods are disclosed for identifying such conjugates by assaying test agents for various cytotoxic responses, including the induction of hyperfusion between neoplastic cells in vitro.
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Citations
36 Claims
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1. An isolated antibody-nucleic acid or peptide-nucleic acid conjugate comprising:
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i) an antibody or peptide that specifically binds to a cellular component of;
a) a tumor cell;
b) tumor vasculature; and
/orc) a component of a tumor microenvironment; and
ii) one or more immunostimulatory nucleic acid sequences (INAS), wherein one or more of the nucleic acid sequences comprise a pathogen-associated molecular pattern (PAMP). - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
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14. A method of treating a neoplastic disease comprising administering to a subject in need thereof, a composition comprising an antibody-nucleic acid conjugate or a peptide-nucleic acid conjugate, wherein the conjugate comprises:
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i) an antibody or a peptide that specifically binds to a cellular component of;
a) a tumor cell, b) tumor vasculature, and/or c) a component of a tumor microenvironment; and
ii) one or more immunostimulatory nucleic acid sequences, wherein one or more of the nucleic acid sequences comprise a pathogen-associated molecular pattern (PAMP). - View Dependent Claims (15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27)
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28. A method of identifying a nucleic acid conjugate which induces cell death, cell maturation, and/or NKG2D ligand dependent signaling comprising:
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i) contacting one or more cells in vitro with a test nucleic acid conjugate containing an antibody that specifically binds to a cellular component of a tumor cell, tumor vasculature, and/or a component of a tumor microenvironment or an integrin derived peptide containing an RGD motif or a CDGRC motif, wherein the antibody or peptide is conjugated toga nucleic acid comprising one or more immunostimulatory nucleic acid sequences, and wherein one or more of the nucleic acid sequences comprise a pathogen-associated molecular pattern (PAMP); and
ii) determining induction of a marker or a phenotypic change in the one or more cells of step (i) in the presence or absence of immune cells, wherein the determined induction or change in the presence of the test nucleic acid conjugate in one or more cells of step (i) is indicative of cell death signaling, cell maturation, and/or NKG2D ligand dependent signaling. - View Dependent Claims (29, 30, 31)
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32. A method of preventing or treating a neoplastic disease or infectious disease comprising administering to a subject in need thereof, a composition comprising an antibody-nucleic acid conjugate, wherein the conjugate comprises:
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i) an antibody that specifically binds to a cellular component of an immune cell or a dendritic cell (DC);
ii) one or more immunostimulatory nucleic acid sequences (INAS), wherein one or more of the nucleic acid sequences comprise a pathogen-associated molecular pattern (PAMP); and
iii) one or more tumor antigens or antigens from an infectious or pathogenic microorganism. - View Dependent Claims (33, 34, 35, 36)
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Specification