Pilot study of Wilms tumor 1-targeted human platelet lysate-induced antigen-presenting cells in advanced solid cancer patients

Introduction: For the wide implementation of dendritic cell-based cancer immunotherapy, a clinical phase I study was conducted to explore its safety and tolerability using Wilms’ tumor 1 (WT1) antigen-targeted human platelet lysate-induced antigen-presenting cells (WT1-HPL-APCs), developed by our team, in patients with advanced solid cancers. Methods: WT1-HPL-APCs were manufactured from apheresed peripheral blood mononuclear cells administered at 4 × 10 7  cells biweekly for three sessions (one course). Adverse events and the induction of WT1-specific T cells (WT1-Cytotoxic T lymphocytes [CTLs]) were evaluated. Furthermore, the potential immunoinducibility of WT1-HPL-APC was examined in vitro and regulatory T cells and monocytic myeloid-derived suppressor cells (M-MDSCs) in the tumor microenvironment (TME) and peripheral blood were assessed to monitor immune cells. Results: The adverse events associated with WT1-HPL-APC vaccination included fever, erythema at the injection site, arthralgia, and chills, all of which were lower than grade 2 in two patients who completed three sessions. The WT1 expression levels and infiltration of CD4 + T cells, CD8 + T cells, and macrophages in the TME differed among the patients. In only one of the two patients with HLA-A*24:02, WT1-HPL-APC induced WT1-CTLs in vitro. Although a WT1-CTL response could not be detected following three sessions of WT1-HPL-APC administration, the percentage of M-MDSCs in the PB tended to decrease. Conclusions: As this pilot study included only three patients with different cancer types, evidence supporting the effectiveness or functionality of WT1-HPL-APCs remains limited. WT1-HPL-APC vaccination was tolerable among patients with advanced solid cancers. Our findings suggest that the immunoinducibility of WT1-HPL-APC vary across individuals and that the preexisting immunosuppressive environment could limit WT1-CTL induction. Future studies are warranted to determine whether WT1-HPL-APC vaccination can improve the patient's immunosuppressive environment and induce WT1-CTLs in combination with optimized chemotherapy or adjuvant therapy in large-scale clinical trials involving multiple doses. Clinical trial registration number: jRCTc040200005.