Volume 2 Supplement 3
PD-L1 expression correlates with immune response in a Phase I trial of CCL21 gene modified dendritic cell therapy in lung cancer
© Lee et al.; licensee BioMed Central Ltd. 2014
Published: 6 November 2014
Anti-tumor immune response in lung cancer patients may be evoked by intra-tumoral (IT) administration of autologous dendritic cells (DC), transduced with a replication-deficient adenoviral (Ad) vector to express the secondary lymphoid chemokine (SLC/CCL21) gene. Here, we evaluated tumor specific immune response after CCL21 gene-modified DC (Ad-CCL21-DC) administration in the context of tumor PD-L1 expression.
Phase I, non-randomized, dose escalating, multi-cohort trial was conducted to enroll patients with Stage IIIB/IV NSCLC. Sixteen patients received 2 vaccinations at a dose of Ad-CCL21-DC (A, B, C, or D; 1 × 106, 5 × 106, 1 × 107, or 3 × 107 cells/injection) by IT injection (days 0 and 7). Peripheral blood was collected for antigen-specific ELISPOT assays, and CT guided needle biopsies of the primary lung cancer were obtained for PD-L1 expression by real time PCR and evaluation of cellular infiltrates by immunohistochemistry.
Peripheral blood of 16 subjects was evaluated by ELISPOT assays. Positive response was defined as 2-fold increase in number of spots above background with an absolute number of >20 spots/2 × 105 cells (positive responder; PR). A mixed response was defined as a positive response with high IFN-γ background expression at day 0 compared to post-vaccine time points (mixed responder; MR). There were 19% (3/16) PR and 19% (3/16) MR for a total of 38% (6/16) total responders. The average PD-L1 gene copy number was 1344 (non-responder; NR) compared to 394 (MR), and 684 (PR) on day 7. Tumor CD8 T cell infiltration was induced in 40% (6/15; all subjects), 33% (3/9; NR), and 50% (3/6; MR & PR).
Intra-tumoral administration of autologous dendritic cells expressing the SLC/CCL21 gene demonstrated that 1) anti-tumor specific immune responses are elicited and correlate with lower PD-L1 expression, and 2) CD8 T cell infiltration into the tumor is induced.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.