Session: 703. Cellular Immunotherapies: Basic and Translational: Poster III
Hematology Disease Topics & Pathways:
Biological therapies, Research, Translational Research, Clinical Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, real-world evidence, Therapies, immunology, Biological Processes, Vaccines
Methods: We determined the humoral and cellular immune responses to SARS-CoV-2 vaccination in 15 patients after CD19.CAR-T cell therapy. In addition, we analyzed 21 patients that were vaccinated before undergoing lymphodepletion and CD19.CAR-T cell treatment for sustained anti-SARS-CoV-2 immunity. Peripheral blood samples were taken before and after SARS-CoV-2 vaccination or before and after CD19.CAR T-cell therapy. Sera were analyzed for the presence of anti-Spike and neutralizing antibodies. SARS-CoV-2 specific T cells were detected by flow cytometric analysis of activation markers with or without prior in vitro stimulation with SARS-CoV-2 Spike and Nucleocapsid antigen.
Results: First, we analyzed 15 patients that previously received CD19.CAR T cells for development of SARS-CoV-2 specific antibodies after vaccination. 13 of 15 patients were still completely B-cell depleted at the time of vaccination, circulating CD19.CAR-T cells could be detected in 10 patients. Only two of the patients showed seroconversion and neutralizing antibodies after vaccination, but most of these patients (13 out of 15) developed Spike-specific T cell responses. Furthermore, we tested 21 patients vaccinated before undergoing lymphodepletion and CD19.CAR-T cell therapy. Interestingly, humoral immune responses remained predominately unchanged in previously vaccinated CD19.CAR-T cell treated patients. Thus, all 10 previously seropositive patients remained positive for S-specific and neutralizing antibodies and 10 of 11 seronegative remained negative. One patient seroconverted which might be explained by an unrecognized infection. Moreover, in patients vaccinated before receiving CD19.CAR-T cells the cellular immune response was sustained throughout the treatment with a constant T-cell response rate.
Conclusions: Taken together, our data confirm strong cellular immune responses to SARS-CoV-2 vaccination in a majority of patients with severe B cell depletion after CD19.CAR-T cell therapy. Since most patients vaccinated before CD19.CAR-T cell treatment showed a humoral and cellular immune response, our study provides evidence for vaccination before CD19.CAR-T cell therapy with subsequent antibody-response detection.
Disclosures: Kremer: Bayer: Current Employment. Blumenberg: Novartis: Honoraria, Research Funding; Celgene: Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Janssen: Research Funding. Harrer: GSK: Consultancy. Mackensen: Novartis: Honoraria; BMS/Celgene: Honoraria; Miltenyi Biomedicine: Honoraria; Kite/Gilead: Honoraria. Subklewe: Roche: Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau; Miltenyi Biotech: Consultancy, Research Funding; Seagen: Research Funding; MorphoSys: Research Funding; Amgen: Research Funding, Speakers Bureau; Gilead: Research Funding, Speakers Bureau; Ichnos: Consultancy; Pfizer: Consultancy, Speakers Bureau; BMS/Celgene: Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Takeda: Consultancy, Research Funding, Speakers Bureau; AvenCell: Consultancy; CDR-Life: Consultancy; Incyte: Consultancy; Molecular Partners: Consultancy.
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