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International Congress of Immunology 2016

Abstract Book


Small airway-on-a-chip: a novel microphysiological system

to study human lung inflammation

in vitro

Hajipouran Benam, K.


, Villenave, R.


, Lucchesi, C.


, Hubeau, C.



Varone, A.


, Ferrante, T.C.


, Weaver, J.C.


, Bahinski, A.


, Hamilton,



, Ingber, D.E.



Harvard University, Wyss Institute for Biologically Inspired

Engineering, Boston, United States,


Pfizer Inc, Cambridge, United


Development of new therapeutics for lung inflammatory and

infectious diseases, such as chronic obstructive pulmonary

disease (COPD) and respiratory viral infections, which are

associated with significant morbidity and mortality, has been

hindered by challenges to study organ-level complexities of

lung inflammation

in vitro


Here, we applied a microengineering technological approach

known as ‘organ-on-chip’ to create a human lung small

airway-on-a-chip that supports full differentiation of a

pseudostratified mucociliary bronchiolar epithelium composed

of cells isolated from normal or diseased donors underlined by

a functional microvascular endothelium, which experiences

continuous blood-like fluid flow. Airway chips lined with well-

differentiated COPD epithelia recapitulated features of the

disease including selective cytokine hypersecretion, increased

neutrophil recruitment, and clinical exacerbations by exposure

to pathogen-mimetic compounds. Using this robust

in vitro

method for modeling human lung inflammatory disorders, it

was possible to detect synergistic effects of lung endothelium

and epithelium on cytokine secretion, identify new biomarkers

of disease exacerbation, and measure responses to anti-

inflammatory compounds that inhibit cytokine-induced

recruitment of circulating neutrophils under physiological

vascular shear. Importantly, the ‘synthetic biology’ nature of

our tissue engineering approach allowed us to independently

control and vary key system parameters that influence organ-

level lung mucosal inflammation.

Thus, the human small airway-on-a-chip offers a powerful

complement to animal models for both analyzing human

pathophysiology and carrying out preclinical drug evaluation.


The GARD assay for potency assessment of skin sensitizing


Forreryd, A., Zeller, K., Lindberg, T., Albrekt, A.-S., Chawade, A.,

Lindstedt, M.

Lund University, Department of Immunotechnology, Medicon

Village, Lund, Sweden

Allergic Contact Dermatitis (ACD) is caused by adverse immune

reactions in the skin and develops upon repeated exposure to

chemical haptens. To reduce exposure, efforts are being made

to develop assays for identification of such



previously developed an assay (GARD) based on a biomarker

signature of 200 mRNAs, identified by transcriptomics of a

myeloid cell-line stimulated with reference chemicals (n=38).

GARD classifies unknown compounds binary, as either skin

sensitizers or non-sensitizers, with an accuracy estimated to

89% (on 39 test chemicals). The aim of the current study is to

broaden applicability domain of GARD to include also potency


We utilized the versatility of analyzing complete transcriptomes

of cells, divided reference samples into potency groups, (CLP-

labeling: no cat, weak=1B, strong=1A) and identified an

alternative signature for prediction of sensitizing potency, using

Random Forest (RF). To shed additional light into the molecular

mechanisms, we also performed a pathway analysis.

A signature comprising 30 genes was identified. The

performance of the signature was validated by cross-validation

and estimated to an accuracy of 85% (no cat), 83% (1A) and 79%

(1B). We also found a correlation between metabolic and cell-

cycle associated pathways and sensitizing potency.

Combining the original and new signature, we present a testing

strategy with an ability not only to identify sensitizing chemicals,

but rather to perform a more complete risk assessment.

Ongoing work focuses on expanding reference chemicals with

an additional 50 chemicals to improve predictive performance,

and to elucidate molecular mechanism involved in sensitization



αHER2/CD3 bifunctional RNA engineered human T cells

specifically eliminate HER2+ gastric cancer

Luo, F., Qian, J., Yang, J., Deng, Y., Zheng, X., Liu, J., Chu, Y.

Fudan University, Shanghai, China

Genetically engineered T cells therapy is a promising strategy

in cancer immunotherapy. One successful strategy is chimeric

antigen receptor (CAR)-T cells therapy, but CARs-restricted on

cell surface and side effects of retrovirus are partial limitations

for CAR-T therapy. An alternative strategy is bispecific T cell

engager (BiTE), but the therapeutic potential of BiTEs is

still limited by the short half-life of antibodies, the lack of

endogenous effector T cells in patients with advanced cancer,

and severe adverse effects. In this study, we developed a novel

secretable human epidermal growth factor receptor 2 (HER2)-

targeting BiTE, αHER2/CD3. These αHER2/CD3 RNA engineered

human T cells persistently secreted αHER2/CD3 fusion proteins,

which were released to help engineered T cell to exhibit HER2-

specific activity, or redirect bystander T cells to HER2+ cancer

cells and even inhibit HER2+ cancer cells proliferation directly.

Additionally, HER2+ tumor-bearing mice treated with the

secretable αHER2/CD3 RNA engineered T cells got a significant

tumor growth inhibition and prolonged survival without

observed adverse effect. Thus, the secretable αHER2/CD3 T

cells have the characteristics of high potency, long term and

low toxicity, which might offer an attractive HER2-targeting

immunotherapy for solid tumors.