{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/19278"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/19278","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Development of a novel antibody molecule for redirected T cell immunity to tumor cells: The bispecific single chain antibody","abstract":"Cancer is the one of the leading causes of death in the United States, and will affect one in three people in their lifetime. In addition to existing treatments, immunotherapy is emerging as a potential fourth tier of cancer therapy. The existence of tumor specific proteins and the production of monoclonal antibodies that bind them allow the specific targeting of cancer cells. A promising use for these anti-tumor antibodies involves redirecting a patient's own cytotoxic T cells (CTL) to specifically kill tumor cells by the use of a bispecific antibody. This approach is achieved through the use of bispecific antibodies that bind the T cell and the tumor cell, triggering the specific elimination of the tumor cell. Despite the success of bispecific antibodies and emergence into clinical trials the optimum method of preparing bispecifics has not been resolved.","abstract_html":"Cancer is the one of the leading causes of death in the United States, and will affect one in three people in their lifetime. In addition to existing treatments, immunotherapy is emerging as a potential fourth tier of cancer therapy. The existence of tumor specific proteins and the production of monoclonal antibodies that bind them allow the specific targeting of cancer cells. A promising use for these anti-tumor antibodies involves redirecting a patient's own cytotoxic T cells (CTL) to specifically kill tumor cells by the use of a bispecific antibody. This approach is achieved through the use of bispecific antibodies that bind the T cell and the tumor cell, triggering the specific elimination of the tumor cell. Despite the success of bispecific antibodies and emergence into clinical trials the optimum method of preparing bispecifics has not been resolved.","abstract_has_math":false,"creators":["Gruber, Meegan Minori"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Biochemistry","degree_department":null,"school":null,"contributors":["Kranz, David M."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-05-07T12:02:34Z","date_published":"2011-05-07T12:02:34Z","updated_at":"2026-07-22T22:25:12Z","subjects":["Biology, Molecular","Chemistry, Biochemistry","Health Sciences, Immunology","Health Sciences, Oncology"],"languages":["eng"],"rights":["Copyright 1996 Gruber, Meegan Minori"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["9780591198812","AAI9712291","(UMI)AAI9712291"],"render_values":[{"text":"9780591198812","href":null,"code":true},{"text":"AAI9712291","href":null,"code":true},{"text":"(UMI)AAI9712291","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/19278","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Kranz, David M."]},{"key":"dc:creator","label":"Author","values":["Gruber, Meegan Minori"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2011-05-07T12:02:34Z","10000-01-01","1996"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biochemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biology, Molecular","Chemistry, Biochemistry","Health Sciences, Immunology","Health Sciences, Oncology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 1996 Gruber, Meegan Minori"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["9780591198812","AAI9712291","(UMI)AAI9712291","http://hdl.handle.net/2142/19278"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Cancer is the one of the leading causes of death in the United States, and will affect one in three people in their lifetime. In addition to existing treatments, immunotherapy is emerging as a potential fourth tier of cancer therapy. The existence of tumor specific proteins and the production of monoclonal antibodies that bind them allow the specific targeting of cancer cells. A promising use for these anti-tumor antibodies involves redirecting a patient's own cytotoxic T cells (CTL) to specifically kill tumor cells by the use of a bispecific antibody. This approach is achieved through the use of bispecific antibodies that bind the T cell and the tumor cell, triggering the specific elimination of the tumor cell. Despite the success of bispecific antibodies and emergence into clinical trials the optimum method of preparing bispecifics has not been resolved.","To begin to engineer more effective bispecific antibodies, we have constructed a novel molecule for redirecting CTL lysis, the bispecific single chain antibody(scFv$\\sb2$). scFv$\\sb2$ were shown to redirect CTL lysis of tumor cells conjugated to a surrogate tumor antigen, the hapten fluorescein, as well as tumor cells that express a true tumor specific protein, erbB-2. In addition, we have demonstrated that a combination of interferon-$\\gamma$ and tumor necrosis factor-$\\alpha$, but neither agent alone, was effective at increasing the susceptibility of some erbB-2$\\sp{+}$ tumors to CTL lysis mediated by scFv$\\sb2$.","The lack of appropriate animal models has hindered the development of bispecific antibodies as in vivo reagents. In anticipation of testing scFv$\\sb2$ in vivo, an animal model with optimal characteristics for testing immunotherapeutics was developed. These double transgenic mice express rearranged 2C T cell receptors (TCR) on a recombination activation gene knockout (RAG$\\sp{-/-}$) background which yielded an immunodeficient strain of mice that contains a monoclonal population of CTLs. The TCR/RAG$\\sp{-/-}$ mice accepted erbB-2$\\sp{+}$ human tumor xenografts. However, the CTLs could be activated to kill target cells in vivo, and should be able to kill tumor cells by antibody redirection. Human tumor xenografts in TCR/RAG$\\sp{-/-}$ mice, therefore, provide a system for evaluating the relative effectiveness of various bispecific antibodies that are currently in development.","Made available in DSpace on 2011-05-07T12:02:34Z (GMT). No. of bitstreams: 2 license.txt: 4922 bytes, checksum: 910b249b4beec47e7ab768910c8f966f (MD5) 9712291.pdf: 6121675 bytes, checksum: ccdeb6349997e20900ea73a1108f0baa (MD5) Previous issue date: 1996","Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Howard Ding (hding2@illinois.edu) on 2011-05-07T14:35:52Z Item is restricted indefinitely.","Restriction data tranferred 2014-07-01T11:14:18-05:00 Original Data Group with Access UIUC Users [automated] Release Date: none Reason: ETDs are only available to UIUC Users without author permission","ETDs are only available to UIUC Users without author permission","U of I Only"]},{"key":"dc:title","label":"Title","values":["Development of a novel antibody molecule for redirected T cell immunity to tumor cells: The bispecific single chain antibody"]}]}],"canonical_facts":{"dc:contributor":["Kranz, David M."],"dc:creator":["Gruber, Meegan Minori"],"dc:date":["2011-05-07T12:02:34Z","10000-01-01","1996"],"dc:description":["Cancer is the one of the leading causes of death in the United States, and will affect one in three people in their lifetime. In addition to existing treatments, immunotherapy is emerging as a potential fourth tier of cancer therapy. The existence of tumor specific proteins and the production of monoclonal antibodies that bind them allow the specific targeting of cancer cells. A promising use for these anti-tumor antibodies involves redirecting a patient's own cytotoxic T cells (CTL) to specifically kill tumor cells by the use of a bispecific antibody. This approach is achieved through the use of bispecific antibodies that bind the T cell and the tumor cell, triggering the specific elimination of the tumor cell. Despite the success of bispecific antibodies and emergence into clinical trials the optimum method of preparing bispecifics has not been resolved.","To begin to engineer more effective bispecific antibodies, we have constructed a novel molecule for redirecting CTL lysis, the bispecific single chain antibody(scFv$\\sb2$). scFv$\\sb2$ were shown to redirect CTL lysis of tumor cells conjugated to a surrogate tumor antigen, the hapten fluorescein, as well as tumor cells that express a true tumor specific protein, erbB-2. In addition, we have demonstrated that a combination of interferon-$\\gamma$ and tumor necrosis factor-$\\alpha$, but neither agent alone, was effective at increasing the susceptibility of some erbB-2$\\sp{+}$ tumors to CTL lysis mediated by scFv$\\sb2$.","The lack of appropriate animal models has hindered the development of bispecific antibodies as in vivo reagents. In anticipation of testing scFv$\\sb2$ in vivo, an animal model with optimal characteristics for testing immunotherapeutics was developed. These double transgenic mice express rearranged 2C T cell receptors (TCR) on a recombination activation gene knockout (RAG$\\sp{-/-}$) background which yielded an immunodeficient strain of mice that contains a monoclonal population of CTLs. The TCR/RAG$\\sp{-/-}$ mice accepted erbB-2$\\sp{+}$ human tumor xenografts. However, the CTLs could be activated to kill target cells in vivo, and should be able to kill tumor cells by antibody redirection. Human tumor xenografts in TCR/RAG$\\sp{-/-}$ mice, therefore, provide a system for evaluating the relative effectiveness of various bispecific antibodies that are currently in development.","Made available in DSpace on 2011-05-07T12:02:34Z (GMT). No. of bitstreams: 2 license.txt: 4922 bytes, checksum: 910b249b4beec47e7ab768910c8f966f (MD5) 9712291.pdf: 6121675 bytes, checksum: ccdeb6349997e20900ea73a1108f0baa (MD5) Previous issue date: 1996","Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Howard Ding (hding2@illinois.edu) on 2011-05-07T14:35:52Z Item is restricted indefinitely.","Restriction data tranferred 2014-07-01T11:14:18-05:00 Original Data Group with Access UIUC Users [automated] Release Date: none Reason: ETDs are only available to UIUC Users without author permission","ETDs are only available to UIUC Users without author permission","U of I Only"],"dc:identifier":["9780591198812","AAI9712291","(UMI)AAI9712291","http://hdl.handle.net/2142/19278"],"dc:language":["eng"],"dc:rights":["Copyright 1996 Gruber, Meegan Minori"],"dc:subject":["Biology, Molecular","Chemistry, Biochemistry","Health Sciences, Immunology","Health Sciences, Oncology"],"dc:title":["Development of a novel antibody molecule for redirected T cell immunity to tumor cells: The bispecific single chain antibody"],"dc:type":["text"],"thesis:degree_discipline":["Biochemistry"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:12Z"}