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BLAST in several species creates unlimited opportunities for antibody selection

BLAST = Diversity:

Complete epitope coverage

  1. Capitalize on BLAST’s application in several species to ensure tolerance is never an issue

  2. The ability to interrogate virtually all IgG’s from all V-gene family members generates thorough baseline target-specific diversity

  3. Take advantage of unique, diverse antibody structure for achieving desired biological function

Mice or “Xeno-mice”

Macaque

Rabbit

Goat

llama

Humans

B-cell source:  Peripheral blood, splenocytes, sentinel node, tumor sample
  1. High throughput screens reveal generated antibody hits to your target

  2. Antibodies are in vivo selected, affinity matured IgG’s, thus you get to take advantage of mother nature’s embedded diversity of V-genes and affinity ranges

  3. On Day 7, the primary concern is selecting the desired antibody

  4. Once selected, if you’re using a non-human source, humanization algorithms provide the best sequences for humanization in nanoseconds.

  5. If the antibody is selected from a human, you’re effectively ready for pre-clinical models

  6. This flexibility allows for iterative processes, ability to rapidly change direction to a more favorable target/epitope, and very high bandwidth

Seven Days:

B-cells

BLAST

Antibodies

..in 7 days

Work at the speed of thought

BLAST is industrialized

  1. Streamlined and optimized to “kit-like” status

  2. If you have PBMC’s from an immune animal freshly drawn or from a cryovial, it can take as little as 40 minutes to start BLASTing a sample. 

  3. The only limitation to the number of targets that can be BLASTed in a year’s time is the assay that accompanies the Day 7 screen. 

  4. If your Day7 screen is developed, BLAST allows one to “work at the speed of thought”, ie. you can set up a BLAST project as quickly as you thought of the experiment.

Antibodies directly from humans

At the moment the desired antibody is isolated, relative to other approaches, it represents the most “de-risked” therapeutic antibody drug lead candidate

As an example, a neutralizing antibody to CMV derived from a titer-positive, disease-free patient:

  1. The antibody is non-toxic at least at the level at which it exists in the serum of the person from which it was derived

  2. The antibody is non-immunogenic since it is fully human

  3. The antibody is efficacious as it is derived from a healthy individual who is not infected with CMV and the antibody binds a known neutralizing epitope

  4. The antibody is functional as it inhibits CMV infection in vitro

  5. The antibody retains the native heavy and light chain and came from a secreting plasmablast which suggests that the pair will have no issues upon manufacture scale up

Fresh

Frozen

BLAST Key Features: