T cell immune response to influenza vaccination when administered prior to and following autologous CAR-T cell therapy.

Background: 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 2019-2020 influenza vaccination.

Methods: Peripheral blood mononuclear cells were isolated from healthy controls and patients who received the 2019-2020 influenza vaccine pre- or post-CD19, CD20 or B cell maturation antigen (BCMA) CAR-T. T cells were expanded in vitro for 10 days with peptide libraries for hemagglutinin (HA) and nucleoprotein (NP) from the 2019-2020 vaccine influenza A strains and analyzed by flow cytometry following IFNγ/TNFα intracellular staining. Antibody response was evaluated by a hemagglutination-inhibition (HAI) assay.

Results: 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 IgG or absolute lymphocyte count and change in CD4+ T cell IFNγ/TNFα response pre- to post-vaccine for the post-CART cohort.

Conclusion: 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.