Download Immune response

The immune response CRO
Founded in 2016
Location
• BioHub at Alderley Park (UK)
Management Team
• Dr. Ir. Robert-Jan Lamers
• Dr. Masih Alam
A CRO offering specialised lab services in the field of immunology:
1.
General immune and bio-analysis of drugs in discovery and research
2.
Immunogenicity analysis - preclinical in vitro human
immune analysis of drugs
TARGET CLIENT GROUPS
- Drug Discovery Companies
- Research Institutions
- CROs for drug analysis
Immunity assays
• Cytokines, growth factors or antigen-specific detection
• Cell mediated immunity
FACS, ELISA
Molecular assays
Histopathology
Microscopy and imaging
Animal models and animal based immunology
Immune Modelling – experimental designs
Mass spectrometry
Translation from preclinical (animal) studies to humans (clinical trials)
needs urgent improvement >> demands preclinical human systems
Immune response (immunogenicity) can be caused by a drug but also by
drug-induced tissue damage
Any drug molecule has the potential to cause unwanted tissue damage
Current immunological risk (immunogenicity) assessment does not
include immune response against tissue damage, causing unsafe drugs
being tested in clinical studies or even being used in treatment
This is a gap in the market!
This is the scope for novel in vitro human immune analytical systems.
Common but currently outweighed due to benefits of ‘risk’ drugs:
• Neuropathy (idiopathic neuropathy)
• Interstitial Lung Disease (DI-ILD)
• Vasculitis
• Drug Induced Lupus (DIL)
• Immune Thrombocytopaenia
• Immune based demyelination
• Myopathy
• >300 drugs are reported to cause DI-ILD (example)
• >2 million cases of adverse drug reactions in the US annually including
100,000 deaths
• 250,000 cases of hospital admissions in the UK annually
• €430M could be saved in the Netherlands if side effects are reduced
Our approach: COMPIT – A NOVEL UNIQUE SYSTEM
•
In vitro human immune model
•
Cell culture systems adapted to test drug-induced damage
•
Focused on novel biomarkers for immune response due to (druginduced) tissue damage using cutting edge analytics (patent foreseen)
•
Incorporates mathematical system to score immunological risk and
predict secondary pathology (patent foreseen)
•
Fits in preclinical studies
Preclinical studies: where does COMPIT fit?
In vitro studies
In vivo studies
COMPIT
General
Characterisation
•
•
•
•
Receptor characterisation
Binding assays
Enzyme inhibition
Cytotoxic activity
Immune
Response
against drug
and druginduced tissue
damage
COMPIT
NOAEL
Mid Dose
Toxicological
studies
Pharmacological
studies
Safety
Efficacy
MTD
Immunological
Safety
Immunological
Safety
(Potential)
Inhibition of
Danger Signals
Dose conversion
• COMPIT can be applied to
• Small molecules
• Large molecules
• Generics and biosimilars
• Potentially predictive (preclinical) of ADA development
• Particularly the research and development of large molecules is evolving and
expanding worldwide >> requiring more immune response analysis
• Regulatory Bodies increasingly seeking/advising analysis of safety based on
new immune markers – these are included in COMPIT
Non Target Tissue
Tissue Damage
Pathology
Disease
ROS – oxidative stress
Metabolites – interference with tissue
Modification of cell biochemistry e.g. covalent binding
ATP depletion or Loss of Ca++ homeostasis
Damaged mitochondria – increased cell permeability
via
Inhalation or
Circulation
P N E U M O C Y T E S
E p i t h e l i a l
A l v e o l a r
a n d
c e l l s
B r o n c h i a l
Dysfunction/Death of Cells
Apoptosis to Necrosis
Compromised Alveolar
Wall
a r e a
Hyaline + Protein rich
Exudate in Alveolar Space
Danger mediated
antigen processing
P R O G R E S S I V E
IMMUNE RESPONSE
Immune mediated
damage + phagocytosis
More examples:
Bleomycin
Amphotericin B
Rituximab
Nitrofurantoin
Maturation and immune
response generated
COMPIT ANALYSIS OF DAMAGE AND IMMUNOGENICITY
Inflammation
Diffuse Alveolar Damage
or
Organising Pneumonia
Hyaline
FIBRIN
Reactive epithelial cells
Scarring
Lung Fibrosis
DI ILD
Better translation from preclinical studies to humans
Reduction of the number of animal tests
A more robust and comprehensive immunologic profile: improved safety
and risk prediction thus reducing human health hazard risk
Drug development can be terminated before costly advanced stages of
drug development: reduced investments in non-viable drugs and
reduced attrition rate
Potential to improve drugs and make non-viable drugs accessible to
patients
Meeting changes to expected regulatory requirements on safety
•
FDA 2014 guideline for ‘Immunogenicity Assessment for Therapeutic Protein Products’
mentions issues related to tolerance to endogenous proteins and autoimmunity
through immune response against endogenous proteins
•
Latest version of EMEA guideline on immunogenicity assessment of biolotechnology
derived therapeutic proteins mentions “while most effort is usually focused on
antibody detection and characterisation as this is often related to clinical safety and
efficacy, cell-mediated responses are also important and their assessment may be
considered by applicants”
•
EMEA meeting (January 2016) “…. a highly interesting and important platform for
pharma and biotech companies that meets an urgent demand”
•
Experienced in immunology and analytical chemistry
•
Access to high-end facilities, professionals and network through location at BioHub
campus
You can work in our lab in the COMPIT project through 2017
and 2018 if your experience fits the requirement of the post
3 month placement period
You will need to bring your own funding for living and travel
Work location is Alderley Park near Macclesfield. You will be
in a large campus where there are many other companies
(mostly discovery and CROs involved in the drug industry)
Purpose:
Skills & Learning:
• Develop and maintain 3D tissue
systems, organoids
• Cell culture, mammalian cells
• Use of hydrogels/matrigels and
specialised tissue growing wells.
• 3 month duration
• Period Sep – Nov 2017 or any other
time
• Location: BioHub, Alderley Park
• 2D and 3D systems, organoids
• Primary and established cells, Stem
cells, media preparation
• Histology, microscopy and imaging
Purpose:
Skills & Learning:
• To extract and measure
immunogenic particles from
damaged tissue in culture.
• Cell culture
• Use of Mass Spec and immunologic
assays for analysis.
• 3 month duration
• Period Sep – Nov 2017 or any time
after that
• Location: BioHub, Alderley Park
• Protein identification and
quantification
• Western blotting, ELISA, MS, RNA
methods
• Experimental designs
Purpose:
Skills & Learning:
• Assess the immunologic events that
follow the tissue damage leading to
an immune activation
• Cell culture, tissue, lymphocytes
• Use of biomolecular and
immunologic assays for analysis.
• 3 month duration
• Period Jun – Aug 2018
• Location: BioHub, Alderley Park
• Protein identification and
quantification
• Western blotting, ELISA, Flow
Cytometry, immunohistochemistry
• Experiment designs
• Statistics
Purpose:
Skills & Learning:
• Design and maintain experiments
that allow interaction of lymphocytes
with damaged tissue
• Cell culture, tissue, lymphocytes
• Use of general and customised cell
culture systems
• Cell migrations
• 2D and 3D cells, organoids
• Microscopy and imaging
• Experiment designs
• 3 month duration
• Period Sep-Nov 2017 and periods in
2018
• Location: BioHub, Alderley Park
Purpose:
Skills & Learning:
• Assimilating and analysing data from
cell culture studies for determining
immune response scores. This will be
crucial to validating the COMPIT
system for preclinical immune
response analysis.
• Mathematical modelling in biological
experiments
• Use of mathematical model designed
by Chester University for translating
experimental data.
• 3 month duration
• Period Jun – Aug 2018
• Location: BioHub, Alderley Park
• Statistics
• Understanding of cell based
biological experiments and cellular
pathways.
• Experimental designs
• Overview of drug toxicology and
preclinical studies
My Contact
DR. MASIH ALAM
IMMUNOSYS LTD
IMMUNDNZ LTD
E. [email protected], [email protected]
www.immunosysltd.com
www.immundnz.com