For Information:
Sue Pondrom
News Bureau lvlanager
( 6 1 9) s s 4 - 8 1 3 3
r20 189-1
NOT FOR RETEASE UNTIL FRIDAY. DEC. 8.
1989
UAJOR TECENOLOGICAL ADVANCE ANNOUNCED
BY RESEARCHINSTITUTE OF SCRIPPS CLINIC
LA JOLLA'
will
enable
I'
to
thousands
possibl-e
has
Institute
of
implemented,
been
discovery
of
of
identify
times
Clinic
by
in
and
more
developed
Scripps
this
A pov/erful
1989
scientists
antibodies
of
CA Dec.
new monoclonals
isolate
scientists
for
than
at
the
California.
accelerate
use in
that
monoclonal
efficiently
La Jo1Ia,
approach should
new technique
is
nohr
Research
When fully
enormously the
research,
pace
medicine
and
today
the
industry.
A description
journal
A.
nscience"
rverson,
and Richard
and
the
by Drs.
Kang,
A. Lerner
of
Mi chel- 1e
university
firm.
of
State
In
past
indispensabLe
been shown to
tool-s
was published
stephen J.
the Research Institute
Drs.
of
stratagene
in
England,
of
rnc.
Kang and Burton are
sheffield
in
Huse, Lakshmi sastry,
Dennis R. Burton,
Alting-tviees
Pennsylvania
the
technique
wil-1iam D.
Angray
biotechnology
the
of
sheila
Benkovic,
Scripps
,
a
Clinic,
La
Jolla
aLso affiliated
and Dr.
with
Benkovic
with
University.
decade,
in
monoclonal
many areas
have great
potential
tjloRE
of
in
antibodies
biological
the
have
research
diagnosis
become
and have
and treatment
PAGE 2 -of
RESEARCH INSTITUTE OP SCRIPPS CLINIC
cancer
individual
of
antibody-producing
and grown in
animal-s
identical
ce1ls
of
cel-l-s.
each
researchers
often
These proteins
diseases.
and other
find
Since
clone
can,
one
tissue
are
products
that
have been isolated
cul-ture
into
populations
the
proteins
antibody
(hence
identical
more
the
cells
by examining
or
are
large
by the
term monoclonal),
numbers of
produce
that
from
or'cl-ones'
secreted
the
of
different
antibodies
clones,
with
specific
properties.
Since
obtained
the
by
mid
the
19 70s,
so-call-ed
antibody-producing
clones
in
forming
culture
that
and
have
particles
been
been
individual
which
and grown as independent
this
a minute
Scripps
by
method
fraction
of
can be induced
examine
antibody.
is
inherently
the
antibody-
proliferate
to
most
departure
production
of
millions
only
In
under
their
bacteria,
it
normally
culture.
MORE
in
bacteria
engineered
bacteria
initial
that
of
of
existing
virus
genes.
found
hundreds
this
antibodies
antibody-producing
procedure.
investigators
of
from
genetically
with
mammalian antibody
By comparison,
at
radical
the
numbers
this
Cl-inic
easily
a
infected
carrying
generated
is
involves
Astonishing
tissue
separated
in
have
conditions.
technique
isolate
only
antibodies
method
However,
an animal
from
The new method
that
are
culture.
in
cell-s
hybridoma
celLs
tissue
inefficient
al-l- monoclonal
in
experiments,
just
days they
each producing
requires
can be
couLd
a different
weeks or
antibody-producing
the
months to
cel1s
in
PAGB 3 --
RESEARCEINSTITUTE OF SCRIPPS CTINIC
The conceptual
basis
moLecul-es are
manufactures
a
nlight"
one of
the
chain
molecule
two
If
light).
these
innovative
in
cells
to
were
formed would likewise
immune system.
each of
four
functional
chains,
identical
all
based on
which
a "heavyn chain
form
a complex of
genes
the
chains
assemble
is
of
approach is
by two genes,
created
two protein
that
(each antibody
antibodies
this
are generated
the way antibodies
Antibody
for
be the
in
and
antibodies
two heavy and
each
same.
cel-1,
the
However, they
are not.
Early
in
the
formation
antibody
producer,
these
undergo
a
of
series
enabl-e them
to
The result
animal
virus,
the body.
to
the
and
this
bacteria,
In short,
mount an antibody
ready antibodies
This
carries
at
various
include
huge
the
estimates,
variability
of
other
their
is
to
rearrangements
and
that
any given
at
thus
antibody-forming
recognize
that
antibody
that
immune system assures that
against
a particular
different
moment is
calLed
repertoire
technique,
of
distinct
the
UORE
drr
ceLls
at
might
invade
be abLe
will
by having
at
invader.
antibodies
the
it
invader
every conceivable
timer
and combat litera1ly
particle
foreign
response to
the
become an
genes independently
chains,
different
be able
as many as 100 mil-Iion
With
light
to
cel-1.
array
or
and
complement of
any given
destined
random alterations
that
a vast
cel1
chain
some of which will
Least
any
carries
of
every
heavy and light
make heavy
molecul-es, unique to
of
antibody
that
an animal
repertoire.
man and other
By
mammals may
antibodies.
Scripps
Clinic
scientists
are
PAGE 4 --
RESEARCE INSTITUTE OF SCRIPPS CLINIC
confident
that
in
repertoire
order
To
step,
first
polymerase
the
resul-t
was two
million
heavy
of
all
the
specific
with
a minute
of
the
series
of
fraction
hybridoma technology.
a
employed
complex
recreate
1iteral1y
antibody
the
chain
reaction
of
and
extract
to
two antibody
the
cell-s.
mouse antibody-forming
gene poo1s,
chains
developed procedure
they. used a recently
a population
from
only
the
to
not
if
particles.
in virus
the
most
antibodies
they
DNA techniques
repertoire
screen
detect
this,
accomplish
recombinant
genes
to
can be observed with
repertoire
ca1led
now
By comparison,
characteristics.
In
can
they
one
the
containing
other
an array
a
similar
in
these
of
number
The
several
of
light
chains.
Although
human white
genes.
mouse cel1s
cells
blood
Thus,
technology
developed
for
hybridoma
method
use
this
is
in
using
task,
random pairs
into
and ki11s
the
Fina1ly,
of
procedure
I"lillions
of
the
The
and has never
of human monoclonals.
developed especially
chain
lambda, a virus
genes were thus
phage were all-owed to
UORE
existing
treatment.
for
gene were
infects
that
"phage" each bearing
chain
antibody
can be
mouse cellS
the production
DNA bacteriophage
modified
and
of
antibodies
one heavy and one light
of heavy and light
the
method over
diagnosis
with
experiments,
as a source
well
this
early
human monoclonal
works wefl
an innovative
bacteria.
combination
that
adapted for
Next,
inserted
equally
clinical
only
been successfully
serve
advantage of
another
hybridoma
used
were
a different
created.
infect
bacteria.
PAGE 5 .-
RBSEARCEINSTITUTB OF SCRIPPS CTINIC
When this
occurs,
genes,
antibody
each
into
becomes a minute
virus
injects
a bacterium.
factory
its
DNA, including
Thus,
capable
of
each infected
the
two
bacterium
a particular
manufacturing
ant ibody.
When these
p1ate,
smal1
bacteria
a
infected
bacteria
appear --
"plaques"
have been killed
single
virus.
contains
clear
by the
Under
antibody
were allowed
the
areas
spreading
condition
molecules
that
indicate
infection
used,
made by
grow on an agar
to
that
where
initiated
plaque
each
during
viruses
by
also
the
infection.
In
an experiment
million
viruses,
producing
single
described
each
a unique
in
capable
antibodyr
the
of
nscience"
infecting
article,
about 15
bacterial
w€r€ generated
from
cells
the
cell-s
and
of
a
mouse.
The Scripps
determine
antibodies
which
thaL
Ivloreover, the
genes from
plaques
recognize
also
devised
among
and bind
the
a simple
million
to particular
assay system to
formed
target
lambda phage used was so designed that
any given
and transferred
production
scientists
to
of that
virus
another
antibody
can be easily
system that
and other
###
extracted
molecul-es.
the
antibody
from the
wou1d aLlow for
genetic
contain
virus
large-scale
manipulations.