KEY TAKEAWAYS
- The ALISON study phase 1 trial aimed to investigate the efficacy of vididencel in HGSOC recurrence in pts who have undergone primary treatment.
- Researchers noticed that vididencel enhanced IFN-γ-secreting T-cell responses, and increased B-cell memory and plasmablast frequencies, suggesting potential for preventing recurrence.
Treatment challenges persist for high-grade serous ovarian cancer (HGSOC) post-debulking and chemotherapy. This phase 1 trial (NCT04739527) investigates vididencel, a cell-based cancer vaccine, aiming to prevent HGSOC recurrence. Vididencel expresses Tumor Associated Antigens (TAA), including WT1 and PRAME. In acute myeloid leukemia (AML) patients (pts), immune responses to these antigens correlated with clinical outcomes. vididencel’s efficacy is evaluated in this pts population.
Given the shared upregulation of these antigens in HGSOC, Annege Vledder and her team aimed to assess the vaccine’s potential in preventing disease recurrence in HGSOC pts population after primary treatment.
The study performed an inclusive analysis on pts with HGSOC post-primary debulking and chemotherapy. Vididencel administration consisted of four biweekly doses (week 0, 2, 4, and 6) at 25 million cells/vaccination, followed by two boosters at week 14 and 18 at 10 million cells/vaccination. Peripheral blood mononuclear cells (PBMC) were collected at week 0, 4, 10, 14, 18, and 22.
IFNγ ELISpot assays were conducted on isolated, frozen PBMC after restimulation with WT1, PRAME, MAGEA3/4, and NY-ESO1. Vaccine-induced T-cell responses (VIR) were calculated as a ≥2-fold increase from the mock-corrected baseline response. Flow cytometry, utilizing a 40-marker panel, was performed to assess the immune profiles of the innate and adaptive immune system. This analysis included activation and exhaustion markers, as well as memory profiles.
About 13 pts with HGSOC were enrolled in the study as of June 23, 2023. Among them, 9 pts completed the treatment phase up to week 22. Notably, all these pts remained alive, although three experienced disease recurrence before week 22.
In the assessment of immune responses to WT1 and PRAME, VIR were observed in 6 out of 8 analyzed pts. Remarkably, responses to NY-ESO1 and MAGEA3/A4, antigens not expressed by vididencel, were induced in 4 out of 8 pts.
Analysis of the immune profile using flow cytometry revealed an augmentation in B-cells post-vaccination. These B-cells exhibited phenotypes resembling memory B-cells (CD19+CD38+CD24-IgM-IgD-CD20dim/- CD27++) or plasmablasts (CD19+ CD38+CD24+IgM+IgD–CD20+CD27–).
The study concluded that vididencel induces increased IFNу secreting T-cells responding to TAA, including those not expressed by vididencel (NY-ESO1 and MAGE A3/A4), suggesting potential antigen spreading. B-cell responses with heightened memory and plasmablast frequencies indicate activation of both innate and adaptive immune systems. Vididencel demonstrates promise in eliciting a broad immune response against ovarian cancer-associated antigens.
The study is sponsored by University Medical Center Groningen
Source: https://jitc.bmj.com/content/11/Suppl_1/A762
Clinical Trial: https://clinicaltrials.gov/study/NCT04739527
Vledder A, Zeeburg H N, Singh S, et al. (2023). “ 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.” Presented at SITC 2023 (Abstract 672).
