Data from Rintatolimod in Advanced Pancreatic Cancer Enhances Antitumor Immunity through Dendritic Cell–Mediated T-Cell Responses

• DOI: 10.1158/1078-0432.c.7403515.v1
• Publication Date: 2024-08-15T07:30:41Z
• Authors: Casper W.F. van E...; Hassana el Haddaoui; Songul Kucukcelebi; Disha Vadgama; Amine Fellah; Dana A.M. Mustafa; Joachim G.J.V. Aerts; Casper H.J. van E...; Marcella Willemsen

<div>AbstractPurpose:<p>Amid the need for new approaches to improve survival in pancreatic ductal adenocarcinoma (PDAC), immune-based therapies have garnered interest. Rintatolimod, a Toll-like receptor 3 (TLR-3) agonist, is potential candidate due its dual impact on restraining PDAC cell functions and boosting antitumor immune response. This study investigates effect of TLR-3 activation through rintatolimod peripheral landscape patients with advanced PDAC.</p>Experimental Design:<p>Paired blood samples 30 PDAC, collected at baseline after 12 intravenous infusions, underwent comprehensive transcriptomic NanoString proteomic flow cytometry profiling. The immunologic factors outcomes was assessed univariate Cox proportional hazards models.</p>Results:<p>Rintatolimod treatment enhances activity levels, particularly involving type 1 conventional dendritic cells (cDC1) T cells. Post-rintatolimod, increased abundance <i>BTLA</i>+ <i>XCR1</i>+ cDC1s <i>CD4</i>+<i>SELL</i>+ correlated improved clinical outcomes. Patients stable disease exhibited pronouncedDCand T-cell gene overexpression. Notably, expression checkpoints PD-L1 PD-L2 decreased post-rintatolimod across all patients. However, those progressive showed genes encoding IDO1 PD-1.</p>Conclusions:<p>This presents compelling evidence immune-stimulatory properties linked rintatolimod. Rintatolimod may break tolerance by enhancing immunity DC-mediated Th-cell responses. Furthermore, our findings lay groundwork investigating synergy between checkpoint inhibitor therapy therapeutic outcomes.</p><p><i><a href="https://aacrjournals.org/cebp/article/doi/10.1158/1078-0432.CCR-24-0938" target="_blank">See related commentary Martínez-Riaño et al., p. 3355</a></i></p></div>