PHASE 2 STUDY OF A NOVEL IMMUNOTHERAPY SL-701 IN ADULTS WITH RECURRENT GBM: IDENTIFICATION OF TREATMENT-INDUCED CD8+CD107A+ CD57+ PD-1- MEMORY T-CELLS THAT ARE ASSOCIATED WITH INCREASED SURVIVAL
Recommended Citation
Peereboom D, Lindsay R, Badruddoja M, Nabors L, Kumthekar P, Lieberman F, Tran D, Phuphanich S, Schiff D, Sherman J, Butowski N, Dunbar E, Fink K, Iwamoto F, Moertel C, Schulder M, Walbert T, Habboubi N, Grzegorzewski K, Brooks C, Reardon DA. PHASE 2 STUDY OF A NOVEL IMMUNOTHERAPY SL-701 IN ADULTS WITH RECURRENT GBM: IDENTIFICATION OF TREATMENT-INDUCED CD8+CD107A+ CD57+ PD-1- MEMORY T-CELLS THAT ARE ASSOCIATED WITH INCREASED SURVIVAL. Neuro-Oncology 2022; 24(Supplement 7):vii67.
Document Type
Conference Proceeding
Publication Date
11-14-2022
Publication Title
Neuro-Oncology
Keywords
bevacizumab, CD4 antigen, CD8 antigen, endogenous compound, programmed death 1 receptor, transcriptome, adult, CD8+ T lymphocyte, conference abstract, controlled study, cytometry, data analysis, female, flow cytometry, gene expression, genetic transcription, helper cell, high throughput sequencing, human, human cell, immunotherapy, kinetics, machine learning, major clinical study, male, memory T lymphocyte, natural killer cell mediated cytotoxicity, overall survival, phase 2 clinical trial, phenotype, signal transduction, T lymphocyte
Abstract
Recurrent glioblastoma (GBM) is an aggressive disease with poor survival and limited treatment options. SL-701 is a novel immunotherapy comprised of synthetic peptides designed to elicit an anti-tumor immune response against GBM antigens IL-13Rα2, ephrinA2, and survivin. Here we describe an 18-color flow cytometry analysis from stage 2 of a Ph2 clinical trial of SL-701+poly-ICLC+bevacizumab (NCT02078648), in which 12-month overall survival (OS) was 50%. Of the 27 patients in stage 2, 24 (89%) developed heterogeneous T-cell responses against 1, 2, or 3 of the SL-701 CD8 peptides. Magnitude and kinetics of peptide responses were variable among these patients with no clear relationship to OS. Therefore, a phenotypic analysis of the T-cell response in all 27 patients was conducted using terraFlow, a unique data analysis approach utilizing machine learning to identify T-cell phenotypes associated with clinical response from all possible combinations of markers. In total, 10,184 unique SL-701 induced phenotypes were measured, including 223 phenotypes (P < 0.05) and 16 core phenotypes that uniquely represent differences between patients with OS above or below 12 months (P < 0.05). 50% of the core phenotypes were CD8+ CD57+ CD107a+ PD-1- SL-701-specific T-cells, which are highly-differentiated memory T-cells primed for cytotoxicity. The frequency of the CD57+ core phenotypes (8%-18%) was enhanced 1.6- to 2.3-fold in patients with an OS > 12 months (P < 0.05). Similarly, 2 core phenotypes identified cytotoxic CD4+ and CD8+ T cells, which were enhanced 1.9- and 2.5-fold in patients with an OS >12 months. The final 6 core phenotypes identified activated CD4+ CD154+ SL-701-specific T-cells (5%-19%) that were enhanced 0.3- to 0.5-fold in patients with an OS < 12 months (P < 0.05), suggesting helper T-cell responses in the absence of cytotoxic T-cell responses are associated with an OS < 12 months. Deep sequencing of SL-701-specific T-cells using whole transcriptome-based molecular cytometry is planned.
Volume
24
Issue
Supplement 7
First Page
vii67
