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Antibody discovery solutions for research, diagnostic and therapeutic goalsBanishree Saha*, Valeria Busygina*, Jamie Campbell, Jacinto Villanueva, Jayne Hammersley, Dele Ashiru, Reem Mahrat, Jennifer Alleman-Sposeto, Yani Chen, Emily Kossa, Joyce YoungAbcam plc, Discovery Drive, Cambridge Biomedical Campus, Cambridge, CB2 0AX, UK
Supporting antibody discovery: research to commercialization
From Spleen via clonal Hybridoma to recombinant RabMAb®: BCMA
Next generation sequencing (NGS) based antibody selection
RabMAb® antibodies via hybridoma
Specific: Proven success for generating specific
antibodies to point mutations or PTMs
Sensitive: High affinity antibodies without polyclonal variability
Pair performance: Provenperformance of antibody pairs in immunoassays
Next Generation
Sequencing-based antibody selection
10-100 fold increase in the number of antibody clones
for evaluation
Support IP portfolio through variant lineage analysis
Insight into the complete antigenic response
AxioMx phage display antibody discovery
Speed: ~6 month binder generation
Antibody engineering: affinitymaturation, CDR grafting,
antibody framework optimization
Toxic antigens: animal-free system to generate binders to
toxins
RabMAb® antibodies via peripheral B-cell cloning
Speed: Sample early bleeds for application specificity,
direct cloning from whole blood
Immunostaining: Workflow optimized for IHC MAbdiscovery
Fusion-free: Due to IP/licensing,
for certain applications, fusion-
free approaches may be desirable
Specific approach for your unique binder
Tailor-Made project design supported by expert scientific team, includes:
– challenging targets– assay support– diverse applications
Collaborative and flexible– milestone-based projects with results-based progression– wrap-around service & collaborative project approaches– flexible licencing and commercial structures
BCMA: A druggable target for multiple myeloma
BCMA
– Promotes proliferation & survival of MM cells
– Associated with immunosuppressive microenvironment
THERAPEUTICS
– CAR-T, T Cell Engagers, ADC
Human/Mouse X-reactive RabMab® identified; binds to both
with sub-nM EC50
anti-BCMA RabMAb® neutralise BAFF binding to BCMA with
sub-nM IC50
-1 1 -1 0 -9 -8 -7 -6-2 0
0
2 0
4 0
6 0
8 0
1 0 0
1 2 0
1 4 0
In h ib it io n o f B A F F b in d in g to B C M A
L o g /M
% o
f m
ax
B O B -1 F 1 -8
B O B -1 F 1 -2 4
R a b b it Ig G
Bottom Top LogIC50 HillSlope IC50
BOB-1 F1-8 7.407 102.2 -9.208 -1.269 6.194e-010
BOB-1 F1-24 1.431 101.9 -9.267 -1.705 5.406e-010
From Peripheral Blood ASC direct to recombinant RabMAb®: PDL1, PD1, CTLA4
T-cell targets for immunotherapy
Completed
targets
Calico Biolabs Inc.
Acquired January 2019
Nature. 480 (7378): 480-489.
T-cell targets for immunotherapy
CAL clones optimized for IHC
– Abcam support complimentary diagnostics needs
– We can provide access to RUO community for your reagent
validation
– Diagnostics supported by our Quality systems, including
ISO13485 and CFR21
– Access to our strategic partnerships to develop your Dx
– Paired single B-cell NGS– Bioinformatic analyses and sequence-based rational selection of leads – Expand IP portfolio surrounding target binding through lineage variant analysis
NGS allows access to entire antibody repertoire
Antibody repertoire after antigen enrichment
Dis
tan
ce
fro
m G
erm
ina
l Ge
ne
s (A
ve
rag
e n
uc
leo
tid
e c
ha
ng
es/
10
0 b
p)
Number of Unique Sequences within Lineage (Log2 Scale)
CDR3 Family (Lineage)
Node size proportional to
lineage size
Lineages recovered by fusion and NGS
Lineages recovered by NGS only
Comprehensive database of antigen-specific binders
that can be parsed experimentally for activity
Breadth of the antigenic response for binder discovery:
– A rational approach for antibody discovery, eliminating redundancy and maximizing diversity in
epitope recognition
– Wide selection of candidate clones to achieve product specification
Accurate VH/VL pairing by single B-cell sequencing
Lineage analysis using depth and breadth