Cell Lines
Tumor and related non-tumor samples
Tissue Biopsies

Source Material

Optional enrichment

ie. membrane preparations

Optional enrichment

LCM or FACS

Genomics
CGH array, SKY
Transcriptomics
Micro-arrays, SAGE
Proteomics
2DE/MS, ICAT
Antibody Technologies
Murine or human mabs, Phage display
Target Function
RNAi
mRNA expression profiling
SAGE, QPCR, in situ hybridization
Protein expression profiling
IHC, TMA, FACS
Antibody Generation
Exterior Surface of tumor
Bioinformatics, FACS

Antibody in vivo activity

Recruit/enhance activity

Effector functions, ADC combo with chemo

Optimization of lead antibody

Humanization/affinity maturation

Antibody Clinical Candidate

Antibody in vitro activity

Growth inhibition, apoptosis, ligand blockade

Target Identification

Target Validation

Therapeutic Antibody Lead Selection

Industry Standard of Practice for Therapeutic Antibody lead Generation

t= time

t = Years and $$$$

t = weeks

Peripheral Blood B-cells
Intratumoral B-cells
BLAST B-cells and screen for desired function
Reconstitute antibody with desired function
Broad pan-reactivity screen
Select Lead and manufacture
Choose lead, small scale-up, target ID,  in vivo test

vs.

BLAST

NCB vs. Industry Standard of Practice

Success in solid tumors:  Interrogation of intratumoral B-cells:

  1. This antibody was discovered from a 3 cm size breast tumor

  2. Took 19 days total to detect and reconstitute this specificity

  3. Hit 15-18 of breast tumor lines tested, equal % in IHC of actual clinical isolates

  4. Appears allogeneic and highly specific for tumor

Success in infectious disease for anti-infectives

  1. Found a neutralizing antibody to influenza virus in 14 days - starting from cells to recombinants

  2. Found a neutralizing antibody to CMV in 17 days - starting from cells to recombinant

  3. Both of these antibodies are in clinical trials today

From human blood to in vitro functional selection to clinical trials

Using BLAST, no technology has come close to putting two antibody therapeutics into clinical trials that took  (in series) less than 2.5 months to find.  Both could’ve easily been done in parallel and taken half the time.  The cycle from bench into humans has been performed for flu, CMV, and HIV.  These antibodies were chosen based on function from individuals who were “negative” for their respective diseases.  The antibodies are non-immunogenic and safe at all doses tested - no surprise there since they came from healthy individuals.

The resulting antibodies highlight the fact that those who endeavor to efficiently and thoroughly sample the human immune repertoire will find antibodies that represent the most up-front “de-risked” antibody drug lead candidates.  They are non immunogenic, they will have no issues with protein folding, they represent an in vivo-selected antibody for fighting disease, and they can be found in less than a months time from PBMC’s to recombinants.
BLAST Advantages: