Clinical Activity of an hTERT-Specific Cancer Vaccine (Vx-001) in "Immune Desert" NSCLC.

Autor: Pateras IS; Department of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece., Kotsakis A; Department of Medical Oncology, University General Hospital of Larissa, 41110 Larissa, Greece., Avgeris M; Laboratory of Clinical Biochemistry-Molecular Diagnostics, 2nd Department of Pediatrics, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece.; Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15771 Athens, Greece., Baliou E; Department of Pathology, Athens Medical Center, 15126 Marousi, Greece., Kouroupakis P; Department of Hematology, Sismanogleion General Hospital of Athens, 15126 Marousi, Greece., Patsea E; Department of Pathology, Metropolitan Hospital, 18547 Cholargos, Greece., Georgoulias V; Hellenic Oncology Research Group, 11474 Athens, Greece., Menez-Jamet J; Vaxon Biotech, 75005 Paris, France., Kinet JP; Vaxon Biotech, 75005 Paris, France.; Department of Pathology, Harvard Medical School, Boston, MA 02215, USA., Kosmatopoulos K; Vaxon Biotech, 75005 Paris, France.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2021 Apr 01; Vol. 13 (7). Date of Electronic Publication: 2021 Apr 01.
DOI: 10.3390/cancers13071658
Abstrakt: Background: Tumors can be separated into immunogenic/hot and non-immunogenic/cold on the basis of the presence of tumor-infiltrating lymphocytes (TILs), the expression of PD-L1 and the tumor mutation burden (TMB). In immunogenic tumors, TILs become unable to control tumor growth because their activity is suppressed by different inhibitory pathways, including PD-1/PD-L1. We hypothesized that tumor vaccines may not be active in the immunosuppressive microenvironment of immunogenic/hot tumors while they could be efficient in the immune naïve microenvironment of non-immunogenic/cold tumors.
Methods: The randomized phase II Vx-001-201 study investigated the effect of the Vx-001 vaccine as maintenance treatment in metastatic non-small cell lung cancer (NSCLC) patients. Biopsies from 131 (68 placebo and 63 Vx-001) patients were retrospectively analyzed for PD-L1 expression and TIL infiltration. TILs were measured as tumor-associated immune cells (TAICs), CD3-TILs, CD8-TILs and granzyme B-producing TILs (GZMB-TILs). Patients were distinguished into PD-L1(+) and PD-L1(-) and into TIL high and TIL low.
Findings: There was no correlation between PD-L1 expression and Vx-001 clinical activity. In contrast, Vx-001 showed a significant improvement of overall survival (OS) vs. placebo in TAIC low (21 vs. 8.1 months, p = 0.003, HR = 0.404, 95% CI 0.219-0.745), CD3-TIL low (21.6 vs. 6.6 months, p < 0.001, HR = 0.279, 95% CI 0.131-0.595), CD8-TIL low (21 vs. 6.6 months, p < 0.001; HR = 0.240, 95% CI 0.11-0.522) and GZMB-TIL low (20.7 vs. 11.1 months, p = 0.011, HR = 0.490, 95% CI 0.278-0.863). Vx-001 did not offer any clinical benefit in patients with TAIC high, CD3-TIL high, CD8-TIL high or GZMB-TIL high tumors. CD3-TIL, CD8-TIL and GZMB-TIL were independent predictive factors of Vx-001 efficacy.
Conclusions: These results support the hypothesis that Vx-001 may be efficient in patients with non-immunogenic/cold but not with immunogenic/hot tumors.
Databáze: MEDLINE
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