Final outcomes analysis of the cell product SQZ-PBMC-HPV Phase 1 trial in incurable HPV16+ solid tumors shows improved overall survival in patients with increased CD8+ T cell tumor infiltration.

Autor: Weaver AN; University of Colorado Comprehensive Cancer Center, Aurora, Colorado, USA., Iams WT; Division of Hematology/Oncology, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA., Park JC; Massachusetts General Hospital, Boston, Massachusetts, USA., Mita M; Cedars-Sinai Medical Center, Los Angeles, California, USA., Holtick U; Department of Internal Medicine, Medical Faculty and University Hospital of Cologne, University of Cologne, Cologne, North Rhine-Westphalia, Germany., Gordon MS; Pinnacle Oncology Hematology, Arizona Center for Cancer Care, HonorHealth Research Institute Clinical Trials Program, Virginia G. Piper Cancer Center, Scottsdale, Arizona, USA., Rodabaugh KJ; University of Nebraska Medical Center, Omaha, Nebraska, USA., Dhani N; University Health Network Princess Margaret Cancer Centre, Toronto, Canada., Neupane P; University of Kansas Cancer Center, Fairway, Kansas, USA., Taylor M; Earle A. Chiles Research Institute, Portland, Oregon, USA., Amanda Duvall E; SQZ Biotechnologies, Watertown, Massachusetts, USA., Jennings J; SQZ Biotechnologies, Watertown, Massachusetts, USA., Miselis NR; SQZ Biotechnologies, Watertown, Massachusetts, USA., Loughhead S; SQZ Biotechnologies, Watertown, Massachusetts, USA., Warren MS; SQZ Biotechnologies, Watertown, Massachusetts, USA., Bernstein H; SQZ Biotechnologies, Watertown, Massachusetts, USA., Klussmann JP; Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty and University Hospital of Cologne, University of Cologne, Cologne, North Rhine-Westphalia, Germany., Baranda J; University of Kansas Cancer Center, Fairway, Kansas, USA., Jimeno A; University of Colorado Comprehensive Cancer Center, Aurora, Colorado, USA.
Jazyk: angličtina
Zdroj: Molecular carcinogenesis [Mol Carcinog] 2024 Aug; Vol. 63 (8), pp. 1421-1428. Date of Electronic Publication: 2024 May 02.
DOI: 10.1002/mc.23738
Abstrakt: Cancer vaccines strive to induce robust, antigen-targeted, T-cell-mediated immune responses but have struggled to produce meaningful regression in solid tumors. An autologous cell vaccine, SQZ-PBMC-HPV, was developed by SQZ Biotechnologies using microfluidic squeezing technology to load PBMCs with HPV16 E6 and E7 antigens in HLA-A*02+ patients. The SQZ-PBMC-HPV-101 Phase 1 trial (NCT04084951) enrolled patients with incurable HPV16+ cancers. Here, we present a post hoc analysis of the relationship between Posttreatment CD8+ T cell infiltration and patient outcomes. SQZ-PBMC-HPV was administered as monotherapy every 3 weeks. Tumor samples were collected pre-dose and post-dose 4 weeks after treatment start. Biomarkers including CD8, MHC-I, E6, E7, GZMB, and Ki67 were evaluated by immunohistochemistry, immunofluorescence, and RNA in situ hybridization, and were correlated with clinical response, survival, and drug product composition. Eighteen patients had paired pre- and post-dose biopsies. Six (33%) had an increase in CD8+ T cell density in tumor parenchyma between screening and C2D8. Patients with increased CD8+ T cell density had improved disease control rate (66.7% vs 16.7%) and median overall survival (606.5 days vs 170.0 days, p = 0.0078). Drug product was significantly enriched for higher T cells and lower monocytes in the increased CD8+ T cell density group. In patients with incurable HPV16+ solid tumors treated with SQZ-PBMC-HPV, an increase in CD8+ T cell density within the tumor parenchyma was associated with superior disease control rate and overall survival. The product composition for patients with increased CD8+ T cell density was enriched for T cells.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
Externí odkaz: