The “take home” message:
For every immune response, a broad repertoire of IgG antibodies is generated to any given target in vivo with a wide range of affinities.   Since 1976 researchers have been trying to harvest from that immune response the best possible antibody against their  target - typically one of highest affinity.  It has been demonstrated that the diverse, in vivo IgG response routinely creates antibodies with highest affinities measuring from single digit pM to high fM.  These antibodies, however, are rare and on the fringe with regard to representation in the IgG pool.  Methods used to sample this vast repertoire in hopes of finding these rare specificities (whether they be ultra high affinity or functional) have fallen short due to the pre-conceived notion that the B-cells need to be immortalized in order to interrogate the antibodies which they secrete - a process that destroys over 95% of the B-cells that are to be interrogated.  The BLAST process has solved this issue by going the opposite direction.  With BLAST, the immune repertoire is preserved allowing for efficient interrogation of virtually the entire repertoire of in vivo affinity matured / selected antibodies for functional, desired therapeutic properties.  Other technical options which are three to four logs less efficient, require a great deal of hope and time in achieving the antibodies of interest.  Hope is not a strategy. BLAST gives you the power of choice and selection.

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BLAST = B-Lymphoblast Activation and Selection Technology

# of IgG specificities

BLAST offers something other technologies don’t - and that is numbers.  By not killing the repertoire with immortalization steps or wiping out a non-immune repertoire (which is by definition limiting) phage library with panning, BLAST experiments can generate in one experiment over 100,000 positives to any given protein target.  Capturing this in vivo response means orders of magnitude more diversity than any other approach and increases greatly the epitope coverage for selection of antibodies with rare functional properties.

Whether sampling the IgG immune repertoire of humans for rare, “needle in the haystack” antibody discovery experiments or sampling several thousand positives from an immune rabbit, mouse, macaque, or llama; the BLAST platform will enable the selection of the most clinically relevant antibody for drug lead candidate status and product development.  When possible, assaying the human repertoire for antibodies of interest is the preferred place to start.  BLAST-derived antibodies from humans generated against viruses are routinely better than those antibodies made in non-human hosts.  These antibodies are also “de-risked” from the stand point of being non-immunogenic (they were derived from a human where the antibody wasn’t immunogenic) and since they are actively present in the serum, the heavy and light chain pair conserved in the BLAST discovery approach virtually ensures proper folding in non-lymphocyte antibody secretion cell lines for production.  They are also already known to be safe at the given titer present in the human from which the antibody was derived since the donor shows no signs of disease. 

In cases where antibodies are not attainable in humans, BLAST has been optimized to work in immune rabbits, mice, macaque, and llama.  These hosts are generally preferred when epitope detection diversity is desired along with elicitation of a wide range of affinities for a given set of epitopes.  With these systems, the desired antibody as a therapeutic is the starting point  and design goals applied to filter through the thousands of target-specific antibodies

BLAST:  The Power of Selection

Efficient sampling enables selection of exceptional therapeutic antibodies

BLAST-derived antibodies from human subjects represent the perfect world scenario for therapeutic antibodies.  By BLAST-ing human IgG memory B-cells, target-specific antibodies or antibodies chosen strictly by function can be rapidly detected (7 days after blood draw) and desired specificities rescued to recombinant status for pre-clinical models in 7-14 more days.  Natural, fully human potent antibodies can be created by BLAST in as little as 21 days. 

The power to choose the desired antibody.....rather than hope for it.

<100 hits

BLAST = >10,000 hits