The CD56 antigen is expressed on several deadly malignancies currently lacking long-term efficacious therapies. Chimeric antigen receptor (CAR) based immunotherapies have shown both safety and efficacy and even a curative ability in clinical trials, laying the foundation for applying CARs to new targets. Using T cells to target a T cell expressed antigen, such as CD56, seems counterintuitive in that the T cells would be susceptible to self-targeting a.k.a. fratricide. However, we expand CD56-specific CAR+ T cells that co-express the CD56 antigen. Since other CARs targeting T cell expressed antigens are hypothesized to be undergoing fratricide, such as the CD38-specific CAR, this unexpected observation of CD56+CD56CAR+ T cells infers that these cells are unique in their survival capacity in a self-targeting scenario. CD56CAR+ T cells have redirected specificity to CD56+ tumor cells and generate anti-tumor responses in neuroblastoma xenograft studies in mice. These CD56CAR+ T cells expand similarly to CAR+ T cells that do not target self-antigen, CD19-specific CAR+ T cells, and do not undergo fratricide. The CD56 antigen co-expressed by CD56CAR+ T cells has diminished ability to stain with the CD56 monoclonal antibody clone N901, which is the epitope where the CAR binds, while the CD56 antigen on CD19CAR+ T cells retains staining. Our data strongly suggest that this epitope loss is not a result of epitope escape of the CD56 antigen. Significant differences in the protein expression profiles of CD19CAR+ and CD56CAR+ T cells, which may be responsible for fratricide evasion of CD56+CD56CAR+ T cells, were observed. Further investigation into these protein differences could delineate a key pathway or responsible for fratricide evasion and be applied in the generation of other CAR based immunotherapies targeting T cell expressed tumor associated antigens. Targeting T cell expressed antigens not only has implications for cancer therapies, but also for treating autoimmune diseases, for the manipulation of transplants or to ablate existing immune cells in a patient as an alternative to chemotherapy.
","abstract_html":"<p>The CD56 antigen is expressed on several deadly malignancies currently lacking long-term efficacious therapies. Chimeric antigen receptor (CAR) based immunotherapies have shown both safety and efficacy and even a curative ability in clinical trials, laying the foundation for applying CARs to new targets. Using T cells to target a T cell expressed antigen, such as CD56, seems counterintuitive in that the T cells would be susceptible to self-targeting a.k.a. fratricide. However, we expand CD56-specific CAR<sup>+</sup> T cells that co-express the CD56 antigen. Since other CARs targeting T cell expressed antigens are hypothesized to be undergoing fratricide, such as the CD38-specific CAR, this unexpected observation of CD56<sup>+</sup>CD56CAR<sup>+</sup> T cells infers that these cells are unique in their survival capacity in a self-targeting scenario. CD56CAR<sup>+</sup> T cells have redirected specificity to CD56<sup>+</sup> tumor cells and generate anti-tumor responses in neuroblastoma xenograft studies in mice. These CD56CAR<sup>+</sup> T cells expand similarly to CAR<sup>+</sup> T cells that do not target self-antigen, CD19-specific CAR<sup>+ </sup>T cells, and do not undergo fratricide. The CD56 antigen co-expressed by CD56CAR<sup>+</sup> T cells has diminished ability to stain with the CD56 monoclonal antibody clone N901, which is the epitope where the CAR binds, while the CD56 antigen on CD19CAR<sup>+</sup> T cells retains staining. Our data strongly suggest that this epitope loss is not a result of epitope escape of the CD56 antigen. Significant differences in the protein expression profiles of CD19CAR<sup>+</sup> and CD56CAR<sup>+</sup> T cells, which may be responsible for fratricide evasion of CD56<sup>+</sup>CD56CAR<sup>+</sup> T cells, were observed. Further investigation into these protein differences could delineate a key pathway or responsible for fratricide evasion and be applied in the generation of other CAR based immunotherapies targeting T cell expressed tumor associated antigens. Targeting T cell expressed antigens not only has implications for cancer therapies, but also for treating autoimmune diseases, for the manipulation of transplants or to ablate existing immune cells in a patient as an alternative to chemotherapy.</p>","abstract_has_math":false,"creators":["Crossland, Denise L"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation (PhD)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Laurence J.N. Cooper, M.D., Ph.D.","Dean A. Lee, M.D., Ph.D.","Bradley McIntyre, Ph.D."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014-08-01T07:00:00Z","date_published":"2014-08-01T07:00:00Z","updated_at":"2026-07-24T05:49:54Z","subjects":["Chimeric Antigen Receptor","CAR","Neural Cell Adhesion Molecule","NCAM","CD56","Fratricide","Autolysis","T cell immunotherapy","self-targeting","CD56CAR","Cancer Biology","Medicine and Health Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/493","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Laurence J.N. Cooper, M.D., Ph.D.","Dean A. Lee, M.D., Ph.D.","Bradley McIntyre, Ph.D."]},{"key":"dc:creator","label":"Author","values":["Crossland, Denise L"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2014-08-11T07:00:00Z"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation (PhD)"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Chimeric Antigen Receptor","CAR","Neural Cell Adhesion Molecule","NCAM","CD56","Fratricide","Autolysis","T cell immunotherapy","self-targeting","CD56CAR","Cancer Biology","Medicine and Health Sciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/493"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The CD56 antigen is expressed on several deadly malignancies currently lacking long-term efficacious therapies. Chimeric antigen receptor (CAR) based immunotherapies have shown both safety and efficacy and even a curative ability in clinical trials, laying the foundation for applying CARs to new targets. Using T cells to target a T cell expressed antigen, such as CD56, seems counterintuitive in that the T cells would be susceptible to self-targeting a.k.a. fratricide. However, we expand CD56-specific CAR+ T cells that co-express the CD56 antigen. Since other CARs targeting T cell expressed antigens are hypothesized to be undergoing fratricide, such as the CD38-specific CAR, this unexpected observation of CD56+CD56CAR+ T cells infers that these cells are unique in their survival capacity in a self-targeting scenario. CD56CAR+ T cells have redirected specificity to CD56+ tumor cells and generate anti-tumor responses in neuroblastoma xenograft studies in mice. These CD56CAR+ T cells expand similarly to CAR+ T cells that do not target self-antigen, CD19-specific CAR+ T cells, and do not undergo fratricide. The CD56 antigen co-expressed by CD56CAR+ T cells has diminished ability to stain with the CD56 monoclonal antibody clone N901, which is the epitope where the CAR binds, while the CD56 antigen on CD19CAR+ T cells retains staining. Our data strongly suggest that this epitope loss is not a result of epitope escape of the CD56 antigen. Significant differences in the protein expression profiles of CD19CAR+ and CD56CAR+ T cells, which may be responsible for fratricide evasion of CD56+CD56CAR+ T cells, were observed. Further investigation into these protein differences could delineate a key pathway or responsible for fratricide evasion and be applied in the generation of other CAR based immunotherapies targeting T cell expressed tumor associated antigens. Targeting T cell expressed antigens not only has implications for cancer therapies, but also for treating autoimmune diseases, for the manipulation of transplants or to ablate existing immune cells in a patient as an alternative to chemotherapy.
"]},{"key":"dc:title","label":"Title","values":["Cd56-Specific T Cells: Using Genetically Engineered T Cells to Redirect Specificity to A T Cell Expressed Antigen"]}]}],"canonical_facts":{"dc:contributor":["Laurence J.N. Cooper, M.D., Ph.D.","Dean A. Lee, M.D., Ph.D.","Bradley McIntyre, Ph.D."],"dc:creator":["Crossland, Denise L"],"dc:date.available":["2014-08-11T07:00:00Z"],"dc:description.abstract":["The CD56 antigen is expressed on several deadly malignancies currently lacking long-term efficacious therapies. Chimeric antigen receptor (CAR) based immunotherapies have shown both safety and efficacy and even a curative ability in clinical trials, laying the foundation for applying CARs to new targets. Using T cells to target a T cell expressed antigen, such as CD56, seems counterintuitive in that the T cells would be susceptible to self-targeting a.k.a. fratricide. However, we expand CD56-specific CAR+ T cells that co-express the CD56 antigen. Since other CARs targeting T cell expressed antigens are hypothesized to be undergoing fratricide, such as the CD38-specific CAR, this unexpected observation of CD56+CD56CAR+ T cells infers that these cells are unique in their survival capacity in a self-targeting scenario. CD56CAR+ T cells have redirected specificity to CD56+ tumor cells and generate anti-tumor responses in neuroblastoma xenograft studies in mice. These CD56CAR+ T cells expand similarly to CAR+ T cells that do not target self-antigen, CD19-specific CAR+ T cells, and do not undergo fratricide. The CD56 antigen co-expressed by CD56CAR+ T cells has diminished ability to stain with the CD56 monoclonal antibody clone N901, which is the epitope where the CAR binds, while the CD56 antigen on CD19CAR+ T cells retains staining. Our data strongly suggest that this epitope loss is not a result of epitope escape of the CD56 antigen. Significant differences in the protein expression profiles of CD19CAR+ and CD56CAR+ T cells, which may be responsible for fratricide evasion of CD56+CD56CAR+ T cells, were observed. Further investigation into these protein differences could delineate a key pathway or responsible for fratricide evasion and be applied in the generation of other CAR based immunotherapies targeting T cell expressed tumor associated antigens. Targeting T cell expressed antigens not only has implications for cancer therapies, but also for treating autoimmune diseases, for the manipulation of transplants or to ablate existing immune cells in a patient as an alternative to chemotherapy.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/493"],"dc:subject":["Chimeric Antigen Receptor","CAR","Neural Cell Adhesion Molecule","NCAM","CD56","Fratricide","Autolysis","T cell immunotherapy","self-targeting","CD56CAR","Cancer Biology","Medicine and Health Sciences"],"dc:title":["Cd56-Specific T Cells: Using Genetically Engineered T Cells to Redirect Specificity to A T Cell Expressed Antigen"],"thesis:degree_level":["Dissertation (PhD)"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:49:54Z"}