Selected articles August 2014:
New epitopes from essential tumor antigens – a step toward more efficient cancer vaccines
Induction of Bcl-xL-specific cytotoxic T lymphocytes in Mice
H. L. Larsen, M. H. Andersen, H. H. Wandall, C. B. Madsen, R. E. Christensen, T. R. Petersen and A. E. Pedersen
In a study by Hjalte Larsen and coworkers, presented in the August issue of Scandinavian Journal of Immunology the group show generation of a robust CD8+ T-cell response against an endogenous target protein, Bcl-XL. Delivering in silico predicted MHC-I antigens in an immunogenic setting by display on in vitro differentiated dendritic cells elicited a specific T-cell response by breaking immunological tolerance. The successful induction of an immune response targeting an endogenous tumor-associated antigen might facilitate the development of more reliable preclinical models of cancer immunotherapy.
Hjalte Larsen was a master student in the group of Dr AE Pedersen at the University of Copenhagen at the time of the study. The project was part of his master thesis and he performed the majority of the experimental work and data analysis as well as designed the experimental setup.
– The most fun part of the work was the successful transition from in silico prediction of target epitopes into the production of a cell-based vaccination strategy that succeeded in inducing specific immunological responses.
Active immunity against tumor-associated antigens to prevent relapse of cancer is a promising, but so far not very efficient therapy, possibly due to clonal escape of tumor cell variants. Tumor-associated antigens are essential for continued tumor cell survival and identification of these will help improve preclinical development of cancer immunotherapy.
Bcl-xL is an anti-apoptotic protein that have been suggested to be an essential tumor antigen. Lack of well-defined murine epitopes have made targeting for the use in cancer vaccines difficult.
Here, the group report the identification of two novel murine tumor-associated epitopes from Bcl-xL.
A recent success of a dendritic cell-like vaccine against metastatic prostate cancer is believed to lead to breakthroughs in vaccination for other types of cancers. However, to develop new cancer vaccines and immunotherapies, preclinical testing in mouse models is essential. In these models the use of endogenous tumor antigens is used, but so far relatively few such antigens have been characterized and tested.
Novel therapeutic approach for auto-inflammatory diseases
Carbon Monoxide–Releasing Molecule-A1 Inhibits Th1/Th17 and Stimulates Th2 Differentiation In vitro
I. Nikolic, M. Vujicic, I. Stojanovic, S. Stosic-Grujicic and T. Saksida
Here, the group from University of Belgrade shows that carbon monoxide has an anti-inflammatory effect through the regulation of the balance between pro-inflammatory Th1/Th17 and anti-inflammatory Th2 cells.
Ivana Nikolic, the first author of the paper is a PhD student at her final year of studying.
– My main responsibility in the work that led to this paper was to perform the experiments in collaboration with other co-authors, to draw the figures and the draft version of the manuscript.
Carbon monoxide is endogenously produced by haeme oxygenase-1 and as profound effects on intracellular signalling processes, generating anti-inflammatory, anti-proliferative and anti-apoptotic effects. CORM-A1 is a boron-containing compound that can release carbon monoxide is such a way to mimic physiological functions of haeme oxygenase-1. In the present study the group studied the immune-modulatory effects of CORM-A1 on murine lymph node-derived T cells in vitro and its influence on T-cell proliferation, activation and differentiation.
– In my opinion, Ivana Nikolic says, the main findings of the paper is that carbon monoxide releasing molecule CORM-A1 affects the Th cells differentiation in vitro, and therefore I feel this study offer novel therapeutic approach in managing Th1/Th17-mediated auto-inflammatory diseases.