Research presentations and publications
Powerpoints for recent research and workshop talks I've given; and a
couple of my recent scientific publications. Includes a review and
bibliography of Immune Responses to Protein Therapeutics (November 2014)
- Up one level
- Bibliography for Immune responses in LSDs
Simon Hunt's references on immune responses in lysosomal storage
disorders (LSDs). These references are by no means a systematic
collection. Rather, they represent papers that seem of interest to
those basic science researchers wishing to understand underlying
mechanisms of antibody production in LSDs and how it might be modulated.
Readers are strongly encouraged to post their own comments and
annotations on these research papers.
- Immune Responses to Protein Therapeutics - ESLSD November 2014
This presentation covers the basic immunology behind antibody formation
during therapies with enzyme therapeutics (ERT) for Lysosomal Storage
Diseases. It considers mechanisms that might be employed to minimise
the formation of these antibodies. A full associated bibliography can be
Please email me if you want any of the Powerpoint slides as a *.pptx
file File: ESLSD_London2014_SVHunt_vFinal.pdf
- Orphan Drugs and Rare Diseases: Book Recommendation.pdf
This book covers the basic science, drug discovery and regulatory
elements behind orphan drugs. It includes a chapter discussing the role
of advocacy groups, and two chapters on enzymes used in treatment of
lysosomal storage disorders.
- Pryde & Palmer "Orphan Drugs and Rare Diseases" Contents Page
These are just the Contents Pages.
- Our 2011 Paper in Immunity
Omilusik et al (2011) "The CaV1.4 Calcium Channel Is a Critical Regulator of T Cell Receptor Signaling and Naive T Cell Homeostasis" Immunity 35: 349-360
"Summary The transport of calcium ions (Ca2+) to the cytosol is essential for immunoreceptor signaling, regulating lymphocyte differentiation, activation, and effector function. Increases in cytosolic-free Ca2+ concentrations are thought to be mediated through two interconnected and complementary mechanisms: the release of endoplasmic reticulum Ca2+ “stores” and “store-operated” Ca2+ entry via plasma membrane channels. However, the identity of molecular components conducting Ca2+ currents within developing and mature T cells is unclear. Here, we have demonstrated that the L-type “voltage-dependent” Ca2+ channel CaV1.4 plays a cell-intrinsic role in the function, development, and survival of naive T cells. Plasma membrane CaV1.4 was found to be essential for modulation of intracellular Ca2+ stores and T cell receptor (TCR)-induced rises in cytosolic-free Ca2+, impacting activation of Ras-extracellular signal-regulated kinase (ERK) and nuclear factor of activated T cells (NFAT) pathways. Collectively, these studies revealed that CaV1.4 functions in controlling naive T cell homeostasis and antigen-driven T cell immune responses."
- Cell Population Array Imaging
This folder contains summary overview material about the CPAI instrument and the idea behind it.
- Perspectives From B Cell Immunology: Fact and Fancy
Published in Int.J.Clin.Pharmacol.Ther., (2009) 47: SUPPL. 1, S86-S99 In
this article, the formation of antibodies during enzyme replacement
therapy (ERT) for lysosomal storage diseases (LSDs) is reviewed in the
light of present-day immunological concepts of immunogenicity and
tolerance. Except in Gaucher disease, anti-enzyme antibodies frequently
form (mainly immunoglobulin G) in patients receiving ERT, though they
tend to wane as treatment continues. If the therapeutic enzyme is
inhibited by antibodies, no significant modification to treatment is
normally warranted, in clear contrast to therapy of hemophilia with
clotting factors. The main adverse consequences of ERT, observed in only
some patients, are sporadic hypersensitivity reactions, which are likely
to be humorally mediated. Some infusion-related reactions are probably
due to antibodies. In order to minimize immunogenicity, infused enzymes
should be deaggregated and administered at low doses. In addition,
inadvertent exposure to co-stimuli that might activate antigen-specific
T or B lymphocytes should be avoided. The presence of cross-reacting
immunological material, such as in patients with low levels or missense
mutations of a gene coding for a lysosomal enzyme, tends to correlate
with immune tolerance to the administered enzyme. There is a need for
reliable biomarkers for therapeutic efficacy: some directions for
further exploration are suggested. In animal models of LSDs, gene
therapy delivered via viral vectors can rectify the lysosomal defect,
and regulatory T cells that suppress antibody formation can be induced.
This is a promising strategy that warrants further investigation in
patients with LSDs.