Unknown

Dataset Information

0

IRX-2, a novel immunotherapeutic, enhances functions of human dendritic cells.


ABSTRACT:

Background

In a recent phase II clinical trial for HNSCC patients, IRX-2, a cell-derived biologic, promoted T-cell infiltration into the tumor and prolonged overall survival. Mechanisms responsible for these IRX-2-mediated effects are unknown. We hypothesized that IRX-2 enhanced tumor antigen-(TA)-specific immunity by up-regulating functions of dendritic cells (DC).

Methodology/principal findings

Monocyte-derived DC obtained from 18 HNSCC patients and 12 healthy donors were matured using IRX-2 or a mix of TNF-?, IL-1? and IL-6 ("conv. mix"). Multicolor flow cytometry was used to study the DC phenotype and antigen processing machinery (APM) component expression. ELISPOT and cytotoxicity assays were used to evaluate tumor-reactive cytotoxic T lymphocytes (CTL). IL-12p70 and IL-10 production by DC was measured by Luminex® and DC migration toward CCL21 was tested in transwell migration assays. IRX-2-matured DC functions were compared with those of conv. mix-matured DC. IRX-2-matured DC expressed higher levels (p<0.05) of CD11c, CD40, CCR7 as well as LMP2, TAP1, TAP2 and tapasin than conv. mix-matured DC. IRX-2-matured DC migrated significantly better towards CCL21, produced more IL-12p70 and had a higher IL12p70/IL-10 ratio than conv. mix-matured DC (p<0.05 for all). IRX-2-matured DC carried a higher density of tumor antigen-derived peptides, and CTL primed with these DC mediated higher cytotoxicity against tumor targets (p<0.05) compared to the conv. mix-matured DC.

Conclusion

Excellent ability of IRX-2 to induce ex vivo DC maturation in HNSCC patients explains, in part, its clinical benefits and emphasizes its utility in ex vivo maturation of DC generated for therapy.

SUBMITTER: Schilling B 

PROVIDER: S-EPMC3567103 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

altmetric image

Publications

IRX-2, a novel immunotherapeutic, enhances functions of human dendritic cells.

Schilling Bastian B   Harasymczuk Malgorzata M   Schuler Patrick P   Egan James J   Ferrone Soldano S   Whiteside Theresa L TL  

PloS one 20130207 2


<h4>Background</h4>In a recent phase II clinical trial for HNSCC patients, IRX-2, a cell-derived biologic, promoted T-cell infiltration into the tumor and prolonged overall survival. Mechanisms responsible for these IRX-2-mediated effects are unknown. We hypothesized that IRX-2 enhanced tumor antigen-(TA)-specific immunity by up-regulating functions of dendritic cells (DC).<h4>Methodology/principal findings</h4>Monocyte-derived DC obtained from 18 HNSCC patients and 12 healthy donors were mature  ...[more]

Similar Datasets

| S-EPMC3721346 | biostudies-literature
| S-EPMC3721331 | biostudies-literature
| S-EPMC5535079 | biostudies-other
| S-EPMC3708464 | biostudies-literature
| S-EPMC4854212 | biostudies-literature
| S-EPMC2749454 | biostudies-literature
| S-EPMC3679715 | biostudies-literature
| S-EPMC3812020 | biostudies-literature
| S-EPMC1933337 | biostudies-literature
| S-EPMC5838419 | biostudies-literature