A PHASE 2 STUDY OF A NOVEL IMMUNOTHERAPY SL-701 IN ADULTS WITH RECURRENT GLIOBLASTOMA: EXPLORING THE PROGNOSTIC VALUE OF TREATMENTINDUCED CD8+CD57+ T-CELLS AS A MARKER FOR SURVIVAL
Recommended Citation
Peereboom D, Lindsay R, Badruddoja M, Nabors L, Kumthekar P, Lieberman F, Schiff D, Sherman J, Butowski N, Dunbar E, Fink K, Iwamoto F, Moertel C, Schulder M, Walbert T, Chattopadhyay P, Habboubi N, Grzegorzewski K, Brooks C, Reardon D. A PHASE 2 STUDY OF A NOVEL IMMUNOTHERAPY SL-701 IN ADULTS WITH RECURRENT GLIOBLASTOMA: EXPLORING THE PROGNOSTIC VALUE OF TREATMENTINDUCED CD8+CD57+ T-CELLS AS A MARKER FOR SURVIVAL. Neuro Oncol 2023; 25(Suppl 5):v56-v56.
Document Type
Conference Proceeding
Publication Date
11-10-2023
Publication Title
Neuro Oncol
Abstract
Recurrent glioblastoma (GBM) remains a challenging disease with limited therapeutic options and poor prognosis. SL-701 is a novel immunotherapy composed of synthetic peptides designed to elicit an anti-tumor immune response against the overexpressed GBM antigens IL-13Rα2, ephrinA2, and survivin. In this study, we present updated findings from a phase 2 clinical trial (NCT02078648) evaluating SL-701+poly-ICLC+bevacizumab, where the 12-month overall survival (OS) was 50%. Using high-parameter flow cytometry, we compared the quality of the treatment induced T-cell response in patients with an OS < 12m (n = 15) versus OS >12m (n = 12). Among the patients assessed, 89% exhibited heterogeneous T-cell responses against SL-701, with no discernible correlation between the response to a specific peptide and survival. Consequently, we focused on identifying other characteristics of the pan-SL701-specific T-cell response with an association to survival. Assessing all time points collected, patients with an OS >12m generated a significantly higher frequency of SL-701-specific CD8 T-cells (79% increase, P < 0.005) and a lower frequency of CD4+ T-cells (36% decrease, P < 0.05) compared to patients with a lower OS. Moreover, the ratio of CD8:CD4 T-cells was 2-fold higher in patients with an OS >12m indicating a CD8-enriched response, whereas patients with an OS < 12m had a lower ratio of CD8:CD4 associated with CD4 enriched responses. Notably, patients with an OS >12m, expressed CD57 (identifying highly cytotoxic, differentiated memory T-cells) on 40% of their T-cells compared to 18% in patients with an OS < 12m (P < 0.05). Furthermore, the ratio of SL-701 specific CD57:CD107A expressing cells trended 20% lower in patients with an OS >12m, indicative of a replicating, cytotoxic T-cell response that is not terminally differentiated. These qualitative differences in the immune response, detectable as early as week 8 post treatment, may serve as biomarkers for monitoring and predicting survival. Deep sequencing of SL-701- specific T-cells is planned.
Volume
25
Issue
Suppl 5
First Page
v56
Last Page
v56
