Clinical analysis of AFFINITY trial: Quantification of tumor-specific antibodies and immune cell activation following Aliya PEF ablation in stage IV cancer patients.

Abstract

e20503 Background: Tumor ablation is generally restricted to control focal disease. There have been rare reports of off-target tumor response (abscopal effect), presumably through the upregulation of tumor-targeting adaptive immunity. Aliya Pulsed Electric Field (PEF) ablation has demonstrated this preclinically, with corresponding increases in antigen-specific CD8 T-cells and tumor-specific antibodies. This report evaluates the immunostimulatory effects of Aliya PEF in patients, focusing on immune cell population dynamics and tumor-specific antibody levels. Methods: In AFFINITY (NCT05890872), patients with stage-IV NSCLC or metastatic cancers to the lungs underwent Aliya PEF ablation followed by first-line standard-of-care (SOC) therapy. Tumor biopsies and blood samples were collected at baseline (pre-PEF) and approximately 3-, 10-, 30-, and 90-days post-PEF; only patients with adequate samples were included in the analysis. ELISA quantified tumor-specific IgG antibodies in patient serum at days 10, 30, 90 bound to tumor biopsy lysate proteins or common tumor antigens (NY-ESO-1, MAGE-A3, MAGE-A4 and WT1). Antibody levels were normalized to day 0, with responders defined as having at least one timepoint with a >15% antibody increase relative to baseline. Flow cytometry (FC) analyzed immune cell populations (days 3, 10, 30), and population changes were evaluated via paired-sample t-test. Results: Tumor-specific IgG analysis of the 19 evaluable patients revealed that 58% (11/19) exhibited increased antibody levels post-PEF. Separately, antibodies to common tumor antigens showed increases in antibodies to NY-ESO-1 (n=5), MAGE-A3 (n=5), MAGE-A4 (n=6), and WT1 (n=4). FC analysis of the 24 evaluable patients revealed immunocyte changes at each timepoint (Table 1). Notably, plasma blasts increased in 71% of patients, peaking at day 10, while plasma cells increased in 59% of patients, peaking at day 30. A strong correlation (R= 0.80) was noted between increased tumor-specific antibodies and plasma cell populations. Conclusions: This data suggests Aliya PEF may induce tumor-specific immunostimulation across diverse cancer histologies, with significant shifts in multiple adaptive immune cell populations and subpopulations as well as increased circulating tumor-specific IgG antibodies in most patients. Future analyses will incorporate SOC therapy’s role and whether PEF-induced changes may invoke systemic disease control and augment systemic therapies. Clinical trial information: NCT05890872 . Mean fold-change vs. baseline (p < 0.05) in circulating immune populations following Aliya ablation (approximate days). Population Day 3 Day 10 Day 30 Activated CD4+ 7.25 9.25 3.1 T regs CD4+ 0.6 0.6 Activated CD8+ 3.9 3.01 3.4 Activated Memory B-cells 5.9 5.3 Switched Memory B-cells 4.3 Plasma blast 6.6 6.1 Plasma cell 7.7