Despite high clinical responses, about 30%-60% of patients with B-cell malignancies relapse following CD19-targeting chimeric antigen receptor (CAR) T cell therapy. CD19 loss is a major cause of relapse and resistance after CD19 CAR T therapy. Dual antigen targeting could overcome resistance due to antigen escape and improve outcomes after CAR T cell therapy. We hypothesized that dual CD19-CD79b CAR T cells will be effective against B cell malignancies by targeting one or both antigens. I have engineered dual CAR targeting CD19 and CD79b antigens under the control of EF1α promoter in a 3rd generation lentiviral vector. The dual CD19-CD79b CAR was composed of CD19 CAR with 4-1BB co-stimulatory domain and CD79b CAR with OX-40 linked by T2A self-cleavable peptide. High transduction efficiency of dual CD19-CD79b CAR was achieved and stable dual CAR expression was observed in both CD4+ and CD8+ T cell subsets. My method of generation of dual CAR T cells attained the optimal CD4+:CD8+ ratio of 1:1 on day 9 after transduction. I demonstrated that both CD19 CAR and CD79b CAR are functional in the dual CAR construct by exhibiting degranulation, proliferation and robust cytotoxic activity against B cell lymphoma and leukemia cell lines expressing either CD19 or CD79b or both. The expression of two distinct CAR molecules in the same cell did not adversely affect T-cell differentiation during the CAR T generation as the phenotype and expression of various inhibitory receptors were similar to untransduced and CD19 CAR-transduced T cells. In summary, dual targeting of CD19 and CD79b could provide a feasible strategy to minimize antigen escape and improve v the efficacy of CAR T treatment for patients with relapsed or refractory B-cell non-Hodgkin lymphoma, hairy cell leukemia and chronic lymphocytic leukemia.
","abstract_html":"<p>Despite high clinical responses, about 30%-60% of patients with B-cell malignancies relapse following CD19-targeting chimeric antigen receptor (CAR) T cell therapy. CD19 loss is a major cause of relapse and resistance after CD19 CAR T therapy. Dual antigen targeting could overcome resistance due to antigen escape and improve outcomes after CAR T cell therapy. We hypothesized that dual CD19-CD79b CAR T cells will be effective against B cell malignancies by targeting one or both antigens. I have engineered dual CAR targeting CD19 and CD79b antigens under the control of EF1α promoter in a 3rd generation lentiviral vector. The dual CD19-CD79b CAR was composed of CD19 CAR with 4-1BB co-stimulatory domain and CD79b CAR with OX-40 linked by T2A self-cleavable peptide. High transduction efficiency of dual CD19-CD79b CAR was achieved and stable dual CAR expression was observed in both CD4+ and CD8+ T cell subsets. My method of generation of dual CAR T cells attained the optimal CD4+:CD8+ ratio of 1:1 on day 9 after transduction. I demonstrated that both CD19 CAR and CD79b CAR are functional in the dual CAR construct by exhibiting degranulation, proliferation and robust cytotoxic activity against B cell lymphoma and leukemia cell lines expressing either CD19 or CD79b or both. The expression of two distinct CAR molecules in the same cell did not adversely affect T-cell differentiation during the CAR T generation as the phenotype and expression of various inhibitory receptors were similar to untransduced and CD19 CAR-transduced T cells. In summary, dual targeting of CD19 and CD79b could provide a feasible strategy to minimize antigen escape and improve v the efficacy of CAR T treatment for patients with relapsed or refractory B-cell non-Hodgkin lymphoma, hairy cell leukemia and chronic lymphocytic leukemia.</p>","abstract_has_math":false,"creators":["Cheng, Xiaoyun","https://orcid.org/0000-0002-0115-711X
"],"institution":null,"degree_name":"Masters of Science (MS)","degree_level":"Thesis (MS)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Sattva S Neelapu","Richard Eric Davis","Laura Bover"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-05-01T07:00:00Z","date_published":"2022-05-01T07:00:00Z","updated_at":"2026-07-24T05:50:24Z","subjects":["dual CD19-CD79b CAR","bicistronic CAR","EF1α promoter","lentiviral transduction","CAR T cell degranulation","CAR T cell cytotoxicity","CAR T cell proliferation","Medicine and Health Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1158","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Sattva S Neelapu","Richard Eric Davis","Laura Bover"]},{"key":"dc:creator","label":"Author","values":["Cheng, Xiaoyun","https://orcid.org/0000-0002-0115-711X
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"]},{"key":"dc:title","label":"Title","values":["Efficacy of Dual Cd19-Cd79B Car In B-Cell Malignancies"]}]}],"canonical_facts":{"dc:contributor":["Sattva S Neelapu","Richard Eric Davis","Laura Bover"],"dc:creator":["Cheng, Xiaoyun","https://orcid.org/0000-0002-0115-711X
"],"dc:date.available":["2023-04-20T07:00:00Z"],"dc:description.abstract":["Despite high clinical responses, about 30%-60% of patients with B-cell malignancies relapse following CD19-targeting chimeric antigen receptor (CAR) T cell therapy. CD19 loss is a major cause of relapse and resistance after CD19 CAR T therapy. Dual antigen targeting could overcome resistance due to antigen escape and improve outcomes after CAR T cell therapy. We hypothesized that dual CD19-CD79b CAR T cells will be effective against B cell malignancies by targeting one or both antigens. I have engineered dual CAR targeting CD19 and CD79b antigens under the control of EF1α promoter in a 3rd generation lentiviral vector. The dual CD19-CD79b CAR was composed of CD19 CAR with 4-1BB co-stimulatory domain and CD79b CAR with OX-40 linked by T2A self-cleavable peptide. High transduction efficiency of dual CD19-CD79b CAR was achieved and stable dual CAR expression was observed in both CD4+ and CD8+ T cell subsets. My method of generation of dual CAR T cells attained the optimal CD4+:CD8+ ratio of 1:1 on day 9 after transduction. I demonstrated that both CD19 CAR and CD79b CAR are functional in the dual CAR construct by exhibiting degranulation, proliferation and robust cytotoxic activity against B cell lymphoma and leukemia cell lines expressing either CD19 or CD79b or both. The expression of two distinct CAR molecules in the same cell did not adversely affect T-cell differentiation during the CAR T generation as the phenotype and expression of various inhibitory receptors were similar to untransduced and CD19 CAR-transduced T cells. In summary, dual targeting of CD19 and CD79b could provide a feasible strategy to minimize antigen escape and improve v the efficacy of CAR T treatment for patients with relapsed or refractory B-cell non-Hodgkin lymphoma, hairy cell leukemia and chronic lymphocytic leukemia.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1158"],"dc:subject":["dual CD19-CD79b CAR","bicistronic CAR","EF1α promoter","lentiviral transduction","CAR T cell degranulation","CAR T cell cytotoxicity","CAR T cell proliferation","Medicine and Health Sciences"],"dc:title":["Efficacy of Dual Cd19-Cd79B Car In B-Cell Malignancies"],"thesis:degree_level":["Thesis (MS)"],"thesis:degree_name":["Masters of Science (MS)"]},"updated_at":"2026-07-24T05:50:24Z"}