Kinoshita Hannah, Walti Carla S, Webber Kathleen, Pezzella Gloria, Jensen-Wachspress Mariah, Lang Haili, Shuey Kiel, Boonyaratanakornkit Jim, Pergam Steven A, Chu Helen Y, Bollard Catherine M, Keller Michael D, Hill Joshua A
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.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington; Infectious Disease and Hospital Epidemiology Division, University Hospital Basel, Basel, Switzerland.
Transplant Cell Ther. 2025 May;31(5):327-338. doi: 10.1016/j.jtct.2025.02.019. Epub 2025 Mar 1.
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.
嵌合抗原受体修饰的T（CAR-T）细胞疗法在复发和难治性恶性肿瘤中的应用越来越广泛。然而，关于这一人群疫苗接种的数据却很缺乏。我们评估了在2019至2020年流感疫苗接种前后，既定队列的CAR-T接受者和健康对照者中的T细胞反应。从健康对照者以及在接受CD19、CD20或B细胞成熟抗原CAR-T之前或之后接种2019至2020年流感疫苗的患者中分离外周血单核细胞。用来自2019至2020年甲型流感疫苗株的血凝素（HA）和核蛋白的肽库在体外将T细胞扩增10天，并在干扰素-γ/肿瘤坏死因子-α（IFNγ/TNFα）细胞内染色后通过流式细胞术进行分析。通过血凝抑制试验评估抗体反应。对29名参与者进行了评估，包括8名免疫功能正常的成年人、7名CAR-T治疗前患者和14名CAR-T治疗后患者。健康对照者接种流感疫苗后的IFNγ/TNFα T细胞反应各不相同，7/8的个体接种后对HA-堪萨斯的反应增强。在CAR-T治疗前队列中，6/7的患者接种疫苗后CD4+ T细胞对HA-布里斯班的反应增强，在CAR-T治疗后90天，3/4可评估的患者中仍可检测到这种反应。6名缺乏抗体反应的患者中有5名对HA-布里斯班表现出T细胞反应。对于CAR-T治疗后队列，自CAR-T给药后的时间、基线免疫球蛋白G或绝对淋巴细胞计数与疫苗接种前后CD4+ T细胞IFNγ/TNFα反应的变化之间没有关联。这些数据表明，在CAR-T治疗前接种疫苗的患者中可引发针对流感疫苗的细胞介导免疫，并在CAR-T治疗后持续存在，填补了因缺乏体液反应而产生的重要空白。
