Cytotoxicity of WT1-reactive T cells against Wilms tumor: An implication for antigen-specific adoptive immunotherapy

• Published in: Bioimpacts Vol. 13; no. 5; pp. 415 - 424
• Main Authors: Monzavi, Seyed Mostafa, Hamidieh, Amir Ali, Vasei, Mohammad, Ai, Jafar, Ahmadbeigi, Naser, Arshadi, Hamid, Muhammadnejad, Samad, Kajbafzadeh, Abdol-Mohammad
• Format: Journal Article
• Language: English
• Published: Tabriz Tabriz University of Medical Sciences 2023; Tabriz University of Medical Sciences (TUOMS Publishing Group)
• Subjects: Acetic acid; Adenomatous polyposis coli; Adoptive immunotherapy; Antibodies; Antigen-presenting cells; Antigens; Blood & organ donations; Bovine serum albumin; Cancer; CD3 antigen; CD4 antigen; CD8 antigen; Chemotherapy; Cloning; Collagenase; Cytokines; Cytotoxicity; cytotoxicity tests; Flow cytometry; Genetic engineering; immunomagnetic separation; Immunotherapy; Isolation media; Lymphocytes; Lymphocytes T; Original; Pediatrics; Peptides; Peripheral blood mononuclear cells; T cell receptors; t-lymphocytes; Tumors; wilms tumor; wt1; Iran; United States > US; Germany
• ISSN: 2228-5660; 2228-5652; 2228-5660
• DOI: 10.34172/bi.2023.27576

Introduction: T cells that recognize WT1 peptides have been shown to efficiently eliminate WT1-expressing tumor cells. This study was designed to investigate the feasibility of isolating WT1-reactive T cells from peripheral blood mononuclear cells (PBMCs) from healthy donors and patients with Wilms tumor, and to assess the cytotoxicity mediated by these cells against Wilms tumor cells (WiTu cells). Methods: WT1-reactive T cells were enriched and isolated by stimulating PBMCs with a WT1 peptide pool and interferon-γ capture-based immunomagnetic separation (IMS). Using the lactate dehydrogenase release assay, the in vitro cytotoxicity of the isolated cells and standard chemotherapy was evaluated on WiTu cells. Results: Higher proportions of WT1-reactive T cells were isolated from patients with Wilms tumor compared to those isolated from HDs. WT1-reactive T cells produced > 50% specific lysis when co-cultured with WT1+ WiTu cells at the highest effector-to-target (E:T) ratio in this study (i.e., 5:1), compared to <23% when co-cultured with WT1- WiTu cells at the same ratio. WT1-reactive T cells showed anti-tumoral activity in a dose-dependent manner and mediated significantly greater cytotoxicity than the non-WT1-reactive fraction of PBMCs on WT1+ WiTu cells. The cytotoxicity of standard chemotherapy was significantly lower than that of WT1-reactive T cells when co-cultured with WT1+ WiTu cells at E:T ratios of 2:1 and 5:1. Conclusion: WT1-reactive T cells can be effectively enriched from the PBMCs of patients with Wilms tumor. Ex vivo generated WT1-reactive T cells might be considered an adoptive immunotherapeutic option for WT1+ Wilms tumors.