Generation of antibodies to tumor antigens and generation of tumor specific complement dependent cytotoxicity by administration of oncolytic vaccinia virus
AssigneesSillajen, Inc., Sillajen Biotherapeutics, Inc.
InventorsDavid Kirn, John Bell, Caroline Breitbach, Anne Moon, Tae-Ho Hwang, Yu Kyoung Lee, Mi-kyung Kim
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Abstract
The present invention relates to methods and compositions for use in inducing tumor-specific antibody mediated complement-dependent cytotoxic response in an animal having a tumor comprising administering to said animal a composition comprising a replication competent oncolytic virus wherein administration of the composition induces in the animal production of antibodies that mediate a CDC response specific to said tumor.
Claims24
A pharmaceutical composition comprising a therapeutically effective amount of polyclonal complement dependent cytotoxic (CDC)-response producing antibodies specific to multiple tumor cell antigens in an animal and a pharmaceutically acceptable carrier and/or diluent, wherein said composition is produced by a method comprising (a) administering to an animal having a tumor an amount of a composition comprising a replication competent oncolytic vaccinia virus effective to induce polyclonal antibodies in said animal that mediate a CDC response specific to said tumor cell antigens and thereafter (b) obtaining a blood or serum sample from the animal containing said CDC-response producing antibodies and/or B cells producing said antibodies (c) confirming the presence of said antibodies and/or B cells producing said antibodies in said blood or serum sample and (d) isolating CDC-response producing antibodies from said blood or serum, expanding said CDC-response producing antibodies ex vivo or producing CDC-response producing antibodies from said B cells and formulating into a composition, wherein the composition comprises polyclonal antibodies that recognize multiple tumor cell antigens selected from the group consisting of RecQ protein-like (DNA helicase Q1-like) (RECQL);
- leptin receptor (LEPR);
- ERBB receptor feedback inhibitor 1 (ERRFI1);
- lysosomal protein transmembrane 4 alpha (LAPTM4A);
- and RAB1B, RAS oncogene family (RAB1B).
A pharmaceutical composition comprising a therapeutically effective amount of polyclonal complement dependent cytotoxic (CDC)-response producing antibodies specific to multiple tumor cell antigens in an animal and a pharmaceutically acceptable carrier and/or diluent, wherein said composition is produced by a method comprising (a) administering to an animal having a tumor an amount of a composition comprising a replication competent oncolytic vaccinia virus effective to induce polyclonal antibodies in said animal that mediate a CDC response specific to said tumor cell antigens and thereafter (b) obtaining a blood or serum sample from the animal containing said CDC-response producing antibodies and/or B cells producing said antibodies (c) confirming the presence of said antibodies and/or B cells producing said antibodies in said blood or serum sample and (d) isolating CDC-response producing antibodies from said blood or serum, expanding said CDC-response producing antibodies ex vivo or producing CDC-response producing antibodies from said B cells and formulating into a composition, wherein the composition comprises polyclonal antibodies that recognize multiple tumor cell antigens selected from the group consisting of RecQ protein-like (DNA helicase Q1-like) (RECQL);
- leptin receptor (LEPR);
- ERBB receptor feedback inhibitor 1 (ERRFI1);
- lysosomal protein transmembrane 4 alpha (LAPTM4A);
- RAB1B, RAS oncogene family (RAB1B);
- CD24;
- homo sapiens thymosin beta 4, X-linked (TMSB4X);
- homo sapiens S100 calcium binding protein A6 (S100A6);
- homo sapiens adenosine A2 receptor (ADORA2B);
- chromosome 16 open reading frame 61 (C16orf61);
- ROD1 regulator of differentiation 1 (ROD1);
- NAD-dependent deacetylase sirtuin-2 (SIR2L);
- tubulin alpha 1c (TUBA1C);
- ATPase inhibitory factor 1 (ATPIF1);
- stromal antigen 2 (STAG2);
- and nuclear casein kinase and cyclin-dependent substrate1 (NUCKS1).
Dependencies are inferred from the claim text.