Lipid A in Cancer Therapy

145 Pages·2010·17.278 MB·English

by  Jean-Françcois Jeannin (auth.), Jean-François Jeannin (eds.)

LipidAin Cancer Therapy
ADVANCES INEXPERIMENTALMEDICINEANDBIOLOGY
EditorialBoard:
NATHANBACK,StateUniversityofNewYorkatBuffalo
IRUNR.COHEN,TheWeizmannInstituteofScience
ABELLAJTHA,N.S.KlineInstituteforPsychiatricResearch
JOHND.LAMBRIS,UniversityofPennsylvania
RODOLFOPAOLETTI,UniversityofMilan
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Lipid A in Cancer Therapy
Editedby
Jean-FrancoisJeannin
TumorImmunologyandImmunotherapyLaboratory
Ecole PractiquedesHautes Etudes
Inserm U866, UniversityofBurgundy,Dijon,France
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LipidAinCancerTherapy,editedbyJean-FrancoisJeannin.LandesBioscience1SpringerScience+Business
Media,LLCdualimprint1Springerseries:AdvancesinExperimentalMedicineandBiology.
ISBN:978-1-4419-1602-0
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Library ofCongressCataloging-in-PublicationData
LipidAincancertherapy1editedbyJean-FrancoisJeannin.
p,;em.-- (Advancesinexperimentalmedicineandbiology;667)
Includesbibliographicalreferencesandindex.
ISBN978-1-4419-1602-0
1. Cancer--Immunotherapy.2. Microbial lipids-Therapeuticuse.3. Endotoxins--Therapeuticuse.
r. Jeannin,Jean-Francois, 1948-II.Series:Advances inexperimental medicine andbiology, v.667.
0065-2598;
[DNLM:1. LipidA--pharmacology.2. LipidA--therapeuticuse.3. Neoplasms-drugtherapy. WI
AD559v.66720091QU85L76052009]
RC27I.I45L572009
616.99'4061--dc22
2009035583
FOREWORD
Cancerremains a major challenge for modem society. Not only does cancer
rank among the first three causes ofmortality in most population groups but also
thetherapeuticoptionsavailableformosttumortypesarelimited.Theexistingones
have limitedefficacy, lackspecificityand their administrationcarry major side ef-
fects.Hence theurgent need fornovel cancertherapies. One ofthemostpromising
avenues inresearchistheuse ofspecific immunotherapy.
Thenotionthattheimmunesystem may have importantanti-tumoreffects has
been around for more than a century now. Every major progress in microbiology
and immunology has been immediately followed by attempts to apply the new
knowledgetothetreatmentofcancer. Progress hasreachedapointwhere itiswell
establishedthat most cancerpatients mount specific T cell responses against their
tumors.Themolecularidentity oftheantigensrecognizedby anti-tumorTcellshas
beenelucidatedandseveralhundreds oftumor-derivedantigenic peptideshavebeen
discovered. Upon recognitionofsuch peptidespresentedby selfMHC molecules,
both CD8 and CD4 Tcells are activated,expandtohigh numbers anddifferentiate
into effective anti-tumoragents.CD8 T cells directly destroy tumor cells and can
causeevenlargetumorstocompletelyregressinexperimentalmousemodels.These
observations have spurredintense researchactivityaimed atdesigningand testing
cancervaccines.
Over 100 years ago Coley successfully used intratumoral injection ofkilled
bacteriato treat sarcomas. The importantanti-tumoreffects observed inafraction
ofthese patients fueled major research efforts. These led to major discoveries in
the 80s and the 90s. It turns out that bacterial lipopolysaccharides stimulate the
production ofmassive amounts ofacytokine still known today as tumor necrosis
factor (TNF-a). They do soby engagementofa rather complexset ofinteractions
culminatingintheligationofaToll-likereceptor,TLR-4. Ensuing signalingthrough
thisreceptorinitiatespotentinnateimmuneresponses. Unfortunatelytheclinicaluse
ofbothTNF-aandLPScannotbegeneralizedduetotheirverynarrow therapeutic
margin.Importantly,synthetic LipidAanalogshavebeenidentifiedthatretainuseful
bioactivityand yetpossess onlymild toxicity.
v
vi Foreword
Therelativelylargebody ofinformationaccumulatedthusfaronthemolecular
and cellularinteractions set in motion by administration ofLPS as well as by the
syntheticLipidAanalogsallowtoplacethisfamilyofbacterially-derivedmolecules
atthecrossroadsbetweeninnateandadaptive immunity. Byvirtue ofthiskeyposi-
tion,thetherapeuticapplicationsbeingpursuedaimatusingthesecompoundseither
asdirect anti-tumoragentsorasvaccineadjuvants.Theclinicalexperienceacquired
sofaronthese twoavenues isasymmetric.Fewclinicaltrialsusing LipidAanalogs
as single anti-canceragents involvingless than 100patients with advancedcancer
have been reported.Incontrast, LipidAhasbeen testedinover300,000individuals
invarious vaccinestrials,includingtherapeuticcancervaccines.
Clearly most ofthe work needed to develop Lipid A as effective anti-cancer
agents and/orasvaccineadjuvantliesaheadinthenearfuture.Thisbookisatimely
contribution and provides a much needed up-to-date overview ofthe chemical,
biologicaland physiological aspects ofLipid A. It shouldbe abeaconto all those
involvedinthis field ofresearch.
Jean-Charles Cerottini, MD
UniversityofLausanne,
FormerDirector, LudwigInstitutefor CancerResearch
LausanneBranch
PedroRomero,MD
UniversityofLausanne,
Member, LudwigInstitutefor CancerResearch
LausanneBranch
ABOUT THE EDITOR...
JEAN-FRAN<;OIS JEANNIN isProfessorofImmunologyat Ecole Practique
des Hautes Etudes (EPHE) and director ofthe EPHE Tumor Immunology and
ImmunotherapyLaboratory,anINSERM(NationalInstituteofHealthand Medical
Research)team.Hismainresearchinterestshaveincludedtheeffects oflipopolysac-
charidesinthetumorimmuneresponseandtheimmunotherapyofcoloncancerwith
LipidA.NowheisinvestigatingmechanismsofimmunotherapywithsyntheticLipid
Aanalogs incancerpatients and animal cancermodels. He is especiallyinterested
in the sensitization oftumor cell death by nitric oxide produced in tumors during
LipidAimmunotherapy.
Jean-FrancoisJeanninhasbeenDean andPresidentoftheLifeSciencesfaculty
ofEPHEand amemberofnumerousscientificorganizations.
vii
PARTICIPANTS
ShizuoAkira Klaus Brandenburg
DepartmentofHost Defense Division ofBiophysics
Research Institute forMicrobial Research Center Borstel
Diseases Leibniz-CenterforMedicine
Osaka University and Biosciences
and Borstel
ERATO Germany
Japan Science andTechnology
Corporation Jean-CharlesCerottini
Osaka UniversityofLausanne
Japan Ludwig Institute forCancer Research
Lausanne
JorgAndra Switzerland
BiophysicsDivision
Research Center Borstel ChristopherW. Cluff
Leibniz-CenterforMedicine GlaxoSmithKlineBiologicals
andBiosciences Hamilton, Montana
Borstel USA
Germany
Thomas Gutsmann
MarcBardou DepartmentofImmunochemistry
Clinical PharmacologyUnit and BiochemicalMicrobiology
andLaboratoryofCardiovascular Research CenterBorstel
ExperimentalPhysiology Leibniz-CenterforMedicine
andPharmacology and Biosciences
Dijon Borstel
France Germany
AliBettaieb Masahito Hashimoto
Tumor Immunology DepartmentofNanostructure
andImmunotherapyLaboratory andAdvancedMaterials
EcolePractique desHautes Etudes Graduate School ofScience
Inserm U866 and Engineering
University ofBurgundy KagoshimaUniversity
Dijon Korimoto,Kagoshima
France Japan
ix
Participants
x
Jean-FrancoisJeannin NiloferQureshi
TumorImmunology DepartmentofBasic MedicalScience
and ImmunotherapyLaboratory SchoolofMedicine
EcolePractiquedesHautes Etudes ShockTraumaResearchCenter
InsennU866 UniversityofMissouri
UniversityofBurgundy Kansas City,Missouri
Dijon USA
France
CatherinePaul
KazuyoshiKawahara TumorImmunology
DepartmentofAppliedMaterial and ImmunotherapyLaboratory
and Life Science InsennU866
CollegeofEngineering UniversityofBurgundy
Kanto GakuinUniversity Dijon
Yokohama,Kanagawa France
Japan
DanieleReisser
ShoichiKusumoto TumorImmunology
SuntoryInstitutefor Bioorganic and ImmunotherapyLaboratory
Research InsennU866
Shimamoto-cho UniversityofBurgundy
Mishima-gun,Osaka Dijon
Japan France
AmandineMartin CherylE.Rockwell
TumorImmunology DepartmentofBasic MedicalScience
and ImmunotherapyLaboratory SchoolofMedicine
InsennU866 ShockTraumaResearchCenter
UniversityofBurgundy UniversityofMissouri
Dijon KansasCity,Missouri
France USA
DavidC. Morrison Pedro Romero
DepartmentofBasic MedicalScience UniversityofLausanne
SchoolofMedicine LudwigInstituteforCancerResearch
ShockTraumaResearchCenter Lausanne
UniversityofMissouri Switzerland
Kansas City,Missouri
USA NejiaSassi
TumorImmunology
MareikeMuller and ImmunotherapyLaboratory
DepartmentofImmunochemistry InsennU866
and BiochemicalMicrobiology UniversityofBurgundy
ResearchCenterBorstel Dijon
Leibniz-CenterforMedicine France
and Biosciences
Borstel
Germany