The Hu-M™ Mouse: A Novel Humanized Mouse Model

The Hu-M™ Mouse: A Novel Humanized Mouse Model

The Hu-M™ Mouse: A Novel Humanized Mouse Model
Antibody Dev. Model!
The Hu-M™ models are extensively
validated for the presence of:
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Human CD19+ B cells
Human CD3+ T cells
Human CD4+ TH cells
Human CD8+ CTL cells
Human CD56+ NK cells
Human CD14+ Macrophages
Human Hematopoietic Progenitors
Improved predictability of efficacy
and safety of drugs for:
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Cancer
Infectious Diseases
Auto-immune Diseases
Stem Cell Malignancies
Cytokine Release Syndrome
Graft vs. Host Disease (GvHD)
Immunogenicity
✦ Reconstituted with pre-qualified hematopoietic stem cells leading to high chimerization.
✦ 8 color flow validation for human lymphocytes in the peripheral blood 10-15 weeks post
engraftment.
✦ Customer tailored flow matrix available.
✦ Special pricing available for first time customers under exploratory study scheme.
HuMurine Technologies, Inc
Ph: 909-859-1050
www.humurine.com
The Hu-M™ Development Process: Generation of the Hu-M™ Mice
The Hu-M™ Development Process: Validation of the Hu-M™ Mice
Humanization Profile in the Peripheral Blood of the Hu-M™ Mouse
104
103
102
10
1
0
105
39.8
0
103
104
<Alexa Fluor 430-A>: Hu CD45
105
Gated on huCD3+ cells!
0.0512
104
103
102
10
101
0
58.6
63.8
5
26.7
0.0772
104
103
102
101
3
0
33.2
0 101
Human Lymphocytes!
(huCD45)!
102
103
104
<PE-A>: Hu CD3
105
0.463
102
103
104
<APC-H7-A>: Hu CD4
105
0
1.31
104
10
3
102
101
0
72.7
0 101
Human T cells!
(huCD3)!
105
Human NK cells!
(huCD56)!
<Pacific Blue-A>: BV421 CD56
0.015
Human CTLs!
(huCD8)!
<FITC-A>: Hu CD8
1.57
Human B cells!
(huCD19)!
<APC-A>: Hu CD19
Murine Lymphocytes!
(muCD45)!
<Alexa Fluor 700-A>: Ms CD45
Gated on huCD45+ cells!
105
0
98.7
0
103
104
<Alexa Fluor 430-A>: Hu CD45
Human TH cells!
(huCD4)!
105
Human Lymphocytes!
(huCD45)!
T Cell Lymphopoiesis in the Spleen of the Hu-M™ Mouse Human Lymphocytes!
(huCD45)!
Human TH cells!
(huCD4)!
Human T cells!
(huCD3)!
Gated on huCD4+ cells!
Human Memory T cells!
(huCD45RO)!
Gated on huCD3+ cells!
Human CTLs!
(huCD8)!
SSC-A!
Murine Lymphocytes!
(muCD45)!
Gated on huCD45+ cells!
Human Naive T cells!
(huCD45RA)!
Human T cells!
(huCD3)!
Murine Lymphocytes!
(muCD45)!
Gated on huCD45+ cells!
Human Lymphocytes!
(huCD45)!
HuMurine Technologies, Inc
Human B cells!
(huCD19)!
Human Memory B cells!
(huCD27)!
B Cell Lymphopoiesis in the Spleen of the Hu-M™ Mouse Gated on huCD19+ cells!
Human Immature B cells!
(huCD38)!
Ph: 909-859-1050
Gated on huCD27+/ huCD38+ cells!
Human Plasma cells!
(huCD138)!
www.humurine.com
The Hu-M™ Platform: Fully Validated to Accelerate Your Pre-Clinical Research
Advantages over existing models:
Reconstituted with validated human hematopoetic stem cells
Robust human hematopoiesis
Cost effective
Cohorts standardized by humanization levels
Available in larger cohorts
Human Cytokines in the Serum of Hu-M™ mice
Treated with Okt-3
IFN-γ
2000
2000
1500
1500
0
d
ee
bl
bl
Pr
Pr
Pr
e-
e-
ee
bl
ePr
Isotype$
16
0
hr
s
ee
d
3
hr
s
16
hr
s
500
hr
s
500
hr
s
bl
ee
d
3
hr
s
16
hr
s
1000
3
1000
hr
s
pg/ml
2500
d
✦ Cytokine Release
Syndrome
✦ Immunity Assessment
✦ Vaccine Development
✦ Graft vs. Host Disease
2500
16
Applications of the
Hu-M™IT platform
pg/ml
Hu-M™ IT Model!
TNF-α
e-
Hu-M™!IT!
3
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Isotype$
Okt3$
Okt3$
Serum was collected at pre-bleed, 3 hrs and 16 hrs post injection of 10 μg of Okt-3 mAb or
IgG2a isotype control. Human cytokine levels of IL-2, TNF-α and IFN-γ were determined
using a Luminex based cytokine detection assay.$
3.5
3.0
os
/L
pG
-C
/L
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om
C
pG
e
-C
/L
ip
BC
os
G
om
e/
ES
AT
-6
2.5
1.0
0.8
0.6
0.4
0.2
0.0
ip
os
om
C
pG
e
-C
/L
ip
BC
os
G
om
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AT
-6
W
0
4.0
ip
5
Spleen
4.5
W
10
5.0
D5
15
pG
✦ Efficacy assessment
of antiviral/bacterial
therapeutics
✦ Pathogenesis Studies
✦ Vaccine Development
20
-C
Applications of the
Hu-M™ID platform
Spleen
D5
Model!
% of HuCD4+ /IL-2 + cells
Hu-M ID
™
C
Hu-M™!ID!
% of HuCD8+ / Granzyme + cells
Human T-cell Mediated Immune Response in
Immunized Hu-M™ mice
In collaboration with Colorado State University, Fort Collins, CO!
HuMurine Technologies, Inc
Ph: 909-859-1050
www.humurine.com
The Hu-M™ Platform: Fully Validated to Accelerate Your Pre-Clinical Research
Hu-M™!AD!
Filovirus Glycoprotein (GP)-specific IgG Response
in the Hu-M™ mice
Hu-M™ AD Model!
Applications of the
Hu-M™AD platform
✦ Evaluating immune
response against
infectious agents or
cancer
✦ Development of fully
humanized antibodies
against unique human
targets
In collaboration with USAMRIID.!
Hu-M™!XENO!
Infiltration of Human CD3+ T cells into MDA-231
Tumors in Hu-M™xeno Mice
Hu-M™ XENO Model!
Applications of the
Hu-M™xeno platform
✦ Development of a
PDX/Humanized
mouse platform
✦ Evaluation of
immuno-modulatory
agents against cancer
Tumor in NOG mice (Day 42) αCD3
Tumor in Hu-M™xeno mice (Day 42) αCD3
Sales and General Inquires:
Prabal Banerjee, Ph.D.
Phone: 909-859-1050
[email protected]
Jenny Rowe, Ph.D.
Phone: 909-859-1366
[email protected]
HuMurine Technologies, Inc
Ph: 909-859-1050
www.humurine.com