T Cell Immune Response to Influenza Vaccination When Administered Prior to and Following Autologous Chimeric Antigen Receptor-Modified T Cell Therapy

Hannah Kinoshita, Center for Cancer and Immunology Research, Children's National Hospital, Washington, District of Columbia; Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia.
Carla S. Walti, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington; Infectious Disease and Hospital Epidemiology Division, University Hospital Basel, Basel, Switzerland.
Kathleen Webber, Center for Cancer and Immunology Research, Children's National Hospital, Washington, District of Columbia.
Gloria Pezzella, Center for Cancer and Immunology Research, Children's National Hospital, Washington, District of Columbia.
Mariah Jensen-Wachspress, Center for Cancer and Immunology Research, Children's National Hospital, Washington, District of Columbia.
Haili Lang, Center for Cancer and Immunology Research, Children's National Hospital, Washington, District of Columbia.
Kiel Shuey, Department of Medicine, University of Washington, Seattle, Washington.
Jim Boonyaratanakornkit, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
Steven A. Pergam, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington; Clinical Research Division and Immunotherapy Integrated Research Center, Seattle, Washington.
Helen Y. Chu, Department of Medicine, University of Washington, Seattle, Washington.
Catherine M. Bollard, Center for Cancer and Immunology Research, Children's National Hospital, Washington, District of Columbia; Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia.
Michael D. Keller, Center for Cancer and Immunology Research, Children's National Hospital, Washington, District of Columbia; Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia.
Joshua A. Hill, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington. Electronic address: jahill3@fredhutch.org.

Document Type

Journal Article

Publication Date

3-1-2025

Journal

Transplantation and cellular therapy

DOI

10.1016/j.jtct.2025.02.019

Keywords

CAR-T; Cellular Immunity; Immunotherapy; Influenza; Vaccine

Abstract

Chimeric antigen receptor-modified T (CAR-T) cell therapies are gaining wider use in relapsed and refractory malignancies. However, data on vaccination in this population is lacking. We evaluated T cell responses in an established cohort of CAR-T recipients and healthy controls before and after 2019 to 2020 influenza vaccination. Peripheral blood mononuclear cells were isolated from healthy controls and patients who received the 2019 to 2020 influenza vaccine pre- or post-CD19, CD20, or B cell maturation antigen CAR-T. T cells were expanded in vitro for 10 days with peptide libraries for hemagglutinin (HA) and nucleoprotein from the 2019 to 2020 vaccine influenza A strains and analyzed by flow cytometry following interferon-γ/tumor necrosis factor-α (IFNγ/TNFα) intracellular staining. Antibody response was evaluated by a hemagglutination inhibition assay. Twenty-nine participants, including eight immunocompetent adults, seven pre-CAR-T, and 14 post-CAR-T patients, were evaluated. IFNγ/TNFα T cell responses after influenza vaccination in healthy controls varied with an increased response to HA-Kansas after vaccination in 7/8 individuals. In the pre-CAR-T cohort, there was a rise in CD4+ T cell response to HA-Brisbane in 6/7 patients after vaccination that remained detectable in 3/4 evaluable patients 90 days post-CAR-T. Five of six patients who lacked an antibody response nonetheless demonstrated a T cell response to HA-Brisbane. There was no association between time since CAR-T administration, baseline immunoglobulin G, or absolute lymphocyte count and change in CD4+ T cell IFNγ/TNFα response pre- to postvaccine for the post-CART cohort. These data demonstrate that cell-mediated immunity to the influenza vaccine can be elicited in patients vaccinated pre-CAR-T and sustained post-CAR-T, filling an important gap from lack of humoral responses.

Department

Pediatrics

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