Nsnrurs
@ TunScnppsRnsnnncu
10666 North Toney PinesRoad
LaJolk, CA 92037
Tehphone619.455.9100
EMBARGOED BY SCIENCE
Wire servicesand broadcastnews,
April 2I, t994,3 p.m. PacificTime
Print media, April 22, 1994
For information:
Robin B. Goldsmirh
(619) 5s4-8t34
#042294
Method of Inhibiting Growth of Malignant Tumors is Determined
by Scientists at The Scripps ResearchInstitute
La Jolla, CA. April 22, 1.994- A novel and potentiallypowerful methodof inhibiting the
growth and metastases
of virnrally all typesof malignanttumorshasbeendevelopedby
investigatorsat The ScrippsResearchInstitute(TSRI) in La Jolla, California. The strategy
involvesliterally starvingtumorsby cutting off their blood supply. Moreover, they suggest
it may be possibleto do this with nothing more than an antibody that targetsblood vessels
enteringtumors.
A paper describingthe experimentalobservationsthat led to this conceptwas publishedin
the April 22 issueof Sciencemagazineby Drs. David A. Cheresh,and PeterC. Brooks, in
the Deparfinentof Immunologyat TSRI, and their collaborator,RichardClark, Jr., M.D.,
in the Departmentof Dermatologyat the StateUniversity of New York at Stony Brook.
In order to grow, thrive, and, ultimately, metastasize,
malignanttumorsmust attractand
becomepervadedwith a rich supplyof blood to provide nourishmentand removewastes.
This is achieved,in pa.t, by the secretionof factorsthat promotenew blood vesselgrowth
in the directionof and into the tumor, a processknown as angiogenesis.
MORE
Page 2 -
METHOD OF II\HIBITING GROWTH OF MALIGNANT TT]MORS
DETERMINED BY TSRI SCIENTISTS
Unfornrnately, extensiveefforts over the past three decadesto deviseways to block the
production or activity of tumor-producedangiogenicfactors have beendisappointing.
Becausemany different molecules,from both normal and tumor cells, are capableof
inducingnew blood vesselgrowth, it hasbeendifficult to block angiogenesis,
althougha
number of compoundscurrently are being examinedfor their effects on the process.
Now, however,Chereshand Brookssuggestthat blocking angiogenesis
may after all be a
highly effective meansof combatingcancer.Ratherthan blocking or inhibiting the
angiogenicsignalsfrom the tumor, they proposeto block the receptionor "reading"of
thosesignalsby blood vesselcells, therebypreventingangiogenesis
from occurringat all.
According to Cheresh,"By inhibiting the processof angiogenesis,we can choke the tumor
from its neededblood supply. When this happens,you can expectthe total annihilationof
the tumor. While work in this area is ongoing, preliminary studiesseemto bear this out. "
The idea arosefrom their studiesof a family of receptormoleculescalled the integrins.
Found on all tissues,integrins receive and respondto molecular signalsof many different
kinds, and in ftrrn control a wide rangeof cellular functions.In blood vessels,Chereshand
Brooks found that one particular integrin, known as VNR, is expressedprimarily on newly
growing blood vesselsproutsbut not at all on adjacent,establishedvessels.This integrin
presumablystimulatesvesselgrowth by promoting adhesionand motility of the cells in the
vesselsto their surroundingsand to tumor tissue.
'We had found somethingdistinct and unique on thesenew vessels,and this gave us the
idea to attemptto block the function of this integrin receptor," Chereshsaid. In earlier
studies, Chereshand his colleagueshad developeda monoclonalantibody that specifically
MORE
Page3 -
METHOD OF IIIHIBITING GROWTH OF MALIGNANT TIJMORS
DETERMINEDBY TSRI SCIENTISTS
blocks the function of the VNR intesrin.
When this antibodywas appliedto a chickenembryoexperimentalmodel sontaining
fragmentsof humantumor they observedthat it virtually preventedblood vesselgrowth
toward the tumor without any effect on the normal vesselsfeeding the embryo. Cheresh
and Brooks believe that this model of angiogenesismight predict what would occur in a
cancerpatientwhen a tumor beginsto grow.
According to Cheresh,uTheconceptis that a monoclonalantibody or other inhibitor of the
VNR integrin might prove to be a novel form of cancertherapy, since it is not directed at
the ever-changingtumor cells as is the casewith current dnrgs, but rather at normal tissues
feeding the tumor. "
Since the Sciencepaperwas written, Chereshand Brooks, togetherwith their TSRI
colleague,Mauricio Rosenfeld,haveshownthat this monoclonalantibodyand other
inhibitors of VNR can block blood vesselgrowth toward tumorsof the lung, colon, and
pancreas.Also, they have begunto test their strategyin other preclinical modelscontaining
human tumors.
###