672 Induction of specific T-cell responses to tumor associated antigens and induction of B-cell responses in ovarian cancer patients by intradermal injection of vididencel

Background

Treatment of high grade serous ovarian cancer (HGSOC) after debulking and chemotherapy remains challenging. This phase 1 trial (NCT04739527) evaluates the use of a cell-based cancer vaccine, vididencel, to prevent disease recurrence after primary treatment. Vididencel expresses Tumor Associated Antigens (TAA), such as WT1 and PRAME, and induced immune responses to these antigens correlated with clinical responses in a study in AML patients. As these antigens are also frequently upregulated in HGSOC, vididencel is evaluated in this patient population.

Methods

Patients with HGSOC after primary debulking and chemotherapy, were given vididencel four times biweekly (week 0, 2, 4 and 6) at 25 million cells/vaccination, followed by 2 boosters at week 14 and 18 at 10 million cells/vaccination. Peripheral blood mononuclear cells (PBMC) were obtained at week 0, 4, 10, 14, 18 and 22. IFNγ ELISpot was performed on isolated, frozen PBMC after restimulation with WT1, PRAME, MAGEA3/4 and NY-ESO1. Vaccine induced T-cell response (VIR) were calculated as ≥2-fold increase of the mock-corrected baseline response. Flow cytometry was being performed using a 40-marker panel to evaluate the immune profiles of innate and adaptive immune system, activation and exhaustion markers and memory profiles.

Results

As of June 23 2023, in total 13 patients have been enrolled, of which 9 had completed the treatment phase (up to week 22). All these patients were still alive and three patients showed disease recurrence before week 22. Immune response assessment to WT1 and PRAME, showed VIR in 6/8 patients analysed. Additionally, NY-ESO1 and MAGEA3/A4 responses, although not expressed by vididencel, were induced in 4/8 patients. Analysis of the immune profile by flow cytometry indicated an increase in B-cells after vaccination, with a phenotypes resembling memory B-cells (CD19⁺CD38⁺⁺CD24^-IgM^-IgD^-CD20^dim/- CD27⁺⁺) or plasmablasts (CD19⁺ CD38⁺CD24⁺IgM⁺IgD^-CD20⁺CD27^-).

Conclusions

IFNу secreting T-cells to TAA expressed by vididencel were increased in the majority of patients. Importantly, VIR to antigens not expressed in these cells, namely NY-ESO1 and MAGE A3/A4, were also increased. These results could indicate antigen spreading by tumor cell lysis, as also previously shown in AML. Except for induced T-cell responses, B-cell responses were observed by increased B-cell memory and plasmablast frequencies. These humoral and cellular responses show activation of both the innate and adaptive immune system. Vididencel thus showed the possibility of induction of a broad immune response to target antigens known to be expressed in ovarian cancer.

Trial Registration

NCT04739527

Ethics Approval

This study was approved by the central committee on research involving human subjects (CCMO) Ethics Board; approval number NL74250.000.20