Intratumoral Plasmid IL12 Expands CD8
Clinical cancer research : an official journal of the American Association for Cancer Research
oregon; portland; chiles
PURPOSE: Triple-negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Antibodies targeting programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) have entered the therapeutic landscape in TNBC, but only a minority of patients benefit. A way to reliably enhance immunogenicity, T-cell infiltration, and predict responsiveness is critically needed.
PATIENTS AND METHODS: Using mouse models of TNBC, we evaluate immune activation and tumor targeting of intratumoral IL12 plasmid followed by electroporation (tavokinogene telseplasmid; Tavo). We further present a single-arm, prospective clinical trial of Tavo monotherapy in patients with treatment refractory, advanced TNBC (OMS-I140). Finally, we expand these findings using publicly available breast cancer and melanoma datasets.
RESULTS: Single-cell RNA sequencing of murine tumors identified a CXCR3 gene signature (CXCR3-GS) following Tavo treatment associated with enhanced antigen presentation, T-cell infiltration and expansion, and PD-1/PD-L1 expression. Assessment of pretreatment and posttreatment tissue from patients confirms enrichment of this CXCR3-GS in tumors from patients that exhibited an enhancement of CD8
CONCLUSIONS: These data show a safe, effective intratumoral therapy that can enhance antigen presentation and recruit CD8 T cells, which are required for the antitumor efficacy. We identify a Tavo treatment-related gene signature associated with improved outcomes and conversion of nonresponsive tumors, potentially even beyond TNBC.
Women & Children
Pathology & Laboratory Medicine
Earle A. Chiles Research Institute
Telli, Melinda L; Nagata, Hiroshi; Wapnir, Irene; Acharya, Chaitanya R; Zablotsky, Kaitlin; Fox, Bernard A; Bifulco, Carlo; Jensen, Shawn M.; Ballesteros-Merino, Carmen; Le, Mai Hope; Pierce, Robert H; Browning, Erica; Hermiz, Reneta; Svenson, Lauren; Bannavong, Donna; Jaffe, Kim; Sell, Jendy; Foerter, Kellie Malloy; Canton, David A; Twitty, Christopher G; Osada, Takuya; Lyerly, H Kim; and Crosby, Erika J, "Intratumoral Plasmid IL12 Expands CD8" (2021). Articles, Abstracts, and Reports. 4421.