Oncolytic Viral Therapy Cancer Treatment

Oncolytic Viral TherapyOncolytic Viral Therapy
Presented by Katherine SawyerPresented by Katherine Sawyer

Oncolytic Viral TherapyOncolytic Viral Therapy
 Definition:Definition:
 ““Onco-” = cancerOnco-” = cancer
 ““-lytic” = killing-lytic” = killing
 Viral = using virusViral = using virus
 Therapy = for treatmentTherapy = for treatment

Onco = CancerOnco = Cancer
 Cancer is……Cancer is……
 Unusual cellUnusual cell
growthgrowth
 Caused byCaused by
genetic mutationgenetic mutation
 Usually in formUsually in form
of tumorof tumor

 Cancer ……Cancer ……
 Unusual cell growthUnusual cell growth
 Caused by genetic mutationCaused by genetic mutation
 Usually in form of tumorUsually in form of tumor
 Blocks immuneBlocks immune
system withsystem with
proteinsproteins
 TakesTakes
resources fromresources from
healthy cellshealthy cells

 Cancer ……Cancer ……
 Unusual cell growthUnusual cell growth
 Caused by geneticCaused by genetic
mutationmutation
 Usually in form of tumorUsually in form of tumor
 Blocks immune systemBlocks immune system
with proteinswith proteins
 Takes resources fromTakes resources from
healthy cellshealthy cells
 Can occur inCan occur in
almost anyalmost any
tissuetissue

Cancer TreatmentsCancer Treatments
 SurgerySurgery
 Remove tumorRemove tumor
 Success only if all of tumor is removed, butSuccess only if all of tumor is removed, but
many cancers metastasize (break andmany cancers metastasize (break and
spread) or have irregular shapes difficult tospread) or have irregular shapes difficult to
removeremove
 Risk associated with any invasive surgeryRisk associated with any invasive surgery

 ChemotherapyChemotherapy
 Use of toxic drugs to kill the cancerUse of toxic drugs to kill the cancer
 Often severe side effects because it also killsOften severe side effects because it also kills
some healthy cellssome healthy cells
 Fairly effective but side effects significantFairly effective but side effects significant
(nausea, fatigue, immune weakness)(nausea, fatigue, immune weakness)

 RadiationRadiation
 Radiation aimed at tumor to kill the tumorRadiation aimed at tumor to kill the tumor
cellscells
 Side effects severe, significant damage toSide effects severe, significant damage to
surrounding tissuesurrounding tissue
 Fairly effective in reducing tumorFairly effective in reducing tumor

 NanotechnologyNanotechnology
 Use carbon or other molecule to carry drug orUse carbon or other molecule to carry drug or
radiation to the tumorradiation to the tumor
 Use shells of cells to carry drugsUse shells of cells to carry drugs
 Attach drugs to molecules that can fit throughAttach drugs to molecules that can fit through
wide cancer blood vessel walls that healthywide cancer blood vessel walls that healthy
cells don’t havecells don’t have
 Magnetically draw device to tumorMagnetically draw device to tumor
 Carry marker for tumor to monitor progressCarry marker for tumor to monitor progress

 Genetic TherapyGenetic Therapy
 Use nanotechnology to re-program cancerUse nanotechnology to re-program cancer
cells’ DNA to make them die young.cells’ DNA to make them die young.

 Oncolytic Viral TherapyOncolytic Viral Therapy
 Genetically modifying a virus so that it killsGenetically modifying a virus so that it kills
cancer cells instead of healthy cellscancer cells instead of healthy cells

Virus: DescriptionVirus: Description
 Protein shell with DNA insideProtein shell with DNA inside
 Requires a host cell to reproduceRequires a host cell to reproduce

Virus: DescriptionVirus: Description
 Requires a host cell to reproduceRequires a host cell to reproduce
 Protein shell with DNA insideProtein shell with DNA inside
 Disease causing agent for diseases likeDisease causing agent for diseases like
measles, herpes, varicella (chicken pox),measles, herpes, varicella (chicken pox),
smallpox, HIV, adeno virus (common cold),smallpox, HIV, adeno virus (common cold),
influenza, rabies, and many othersinfluenza, rabies, and many others
 Unlike bacteria, there are no beneficialUnlike bacteria, there are no beneficial
viruses (always kills its host)viruses (always kills its host)

Virus: StructureVirus: Structure
 Protein shell called aProtein shell called a
capsid contains DNAcapsid contains DNA
 Arrangement of oneArrangement of one
or more protein fibersor more protein fibers
or spikes for bondingor spikes for bonding
with host cellwith host cell

Virus: StructureVirus: Structure

Virus: ReproductionVirus: Reproduction
 Attaches to host cell with spikes orAttaches to host cell with spikes or
filamentsfilaments

 Once attached, it pushes its DNA inside the cell,Once attached, it pushes its DNA inside the cell,
 Uses the cell’s DNA as buildingUses the cell’s DNA as building blocksblocks for its newfor its new
DNADNA
 New virus breaks through cell wallNew virus breaks through cell wall

Oncolytic Viral Therapy: MethodOncolytic Viral Therapy: Method
 Choose a resilient virus that is successfulChoose a resilient virus that is successful
in human bodyin human body
 MeaslesMeasles
 HerpesHerpes
 Adeno virus (common cold)Adeno virus (common cold)
 Influenza virusInfluenza virus
 SmallpoxSmallpox

in the human bodyin the human body
 Splice DNA into virus DNA that codes forSplice DNA into virus DNA that codes for
a protein that bonds well and is attracteda protein that bonds well and is attracted
to tumor’s proteinto tumor’s protein

in the human bodyin the human body
 Splice DNA into virus DNA that codes forSplice DNA into virus DNA that codes for
a protein that bonds well and is attracteda protein that bonds well and is attracted
to tumor’s proteinto tumor’s protein
 Inject the modified viruses into tumor siteInject the modified viruses into tumor site

 Choose a resilient virus that is successful in theChoose a resilient virus that is successful in the
human bodyhuman body
 Splice DNA into virus DNA that codes for aSplice DNA into virus DNA that codes for a
protein that bonds well and is attracted toprotein that bonds well and is attracted to
tumor’s proteintumor’s protein
 Inject the modified viruses into tumor siteInject the modified viruses into tumor site
 Used alone or in conjunction with chemotherapy,Used alone or in conjunction with chemotherapy,
radiation, surgery, and nanotechnologyradiation, surgery, and nanotechnology

Oncolytic Viral Therapy:Oncolytic Viral Therapy:
ChallengesChallenges
 Genetic modification to match specificGenetic modification to match specific
cancercancer
 Main challenge is patient’s own immuneMain challenge is patient’s own immune
system killing the virus before the virussystem killing the virus before the virus
can kill the cancer.can kill the cancer.

ChallengesChallenges
 Genetic modification to match specific cancerGenetic modification to match specific cancer
 Main challenge is patient’s own immune systemMain challenge is patient’s own immune system
killing the virus before the virus can kill thekilling the virus before the virus can kill the
cancer.cancer.
 SolutionsSolutions
 Fast acting virusFast acting virus
 Protection from immune systemProtection from immune system
 Protection of virus on the virusProtection of virus on the virus
 Block immune systemBlock immune system

Oncolytic Viral Therapy: TimelineOncolytic Viral Therapy: Timeline
 1970’s Mayo Clinic noted that measles1970’s Mayo Clinic noted that measles
patients with cancer experienced tumorpatients with cancer experienced tumor
reductionreduction
 1980’s research proposals1980’s research proposals
 Human genome project, other geneticHuman genome project, other genetic
researchresearch
 2005 first clinical trials of oncolytic viral2005 first clinical trials of oncolytic viral
therapytherapy

Oncolytic Viral Therapy: TrialsOncolytic Viral Therapy: Trials
 Measles VirusMeasles Virus
 Most successful trialMost successful trial
 Brain cancer –highBrain cancer –high
success rate (Mayosuccess rate (Mayo
Clinic)Clinic)
 Multiple myelomaMultiple myeloma
--previously incurable--previously incurable
bone cancer (Mayobone cancer (Mayo
Clinic)Clinic)

 Seneca ValleySeneca Valley
VirusVirus
 Developed byDeveloped by
NeoptrixNeoptrix
 Successful atSuccessful at
destroying smalldestroying small
cell lung cancercell lung cancer

 Adeno Virus (coldAdeno Virus (cold
virus)virus)
 Designed to kill cellsDesigned to kill cells
with common mutationwith common mutation
of colon cancerof colon cancer
(unidentified research(unidentified research
group)group)
 Successful withSuccessful with
breast, liver, skinbreast, liver, skin
cancers (University ofcancers (University of
Birmingham)Birmingham)

 Herpes VirusHerpes Virus
 Variety of tumorsVariety of tumors
(Baylor University in(Baylor University in
San Diego withSan Diego with
Immusol in China)Immusol in China)
 50% success rate with50% success rate with
pancreatic cancerpancreatic cancer
previously a nearlypreviously a nearly
untreatable canceruntreatable cancer
(Nagoya University,(Nagoya University,
Japan)Japan)

Specialized TrialsSpecialized Trials
 Measles VirusMeasles Virus
 FusogenicFusogenic
MembraneMembrane
GlycoproteinsGlycoproteins
 (FMG)(FMG)
 Causes cancerCauses cancer
cells to fuse withcells to fuse with
each other and dieeach other and die
 (Mayo Clinic)(Mayo Clinic)

SpecializedTrialsSpecializedTrials
 Intravenous VS VirusIntravenous VS Virus
 First trial of intravenous oncolytic viralFirst trial of intravenous oncolytic viral
therapy(others used injection at tumor site)therapy(others used injection at tumor site)
 Potential to “chase down” metastasized cellsPotential to “chase down” metastasized cells
 (University of Calgary)(University of Calgary)

 Polymer-coated Adeno VirusPolymer-coated Adeno Virus
 Protects the oncolytic virus from patientProtects the oncolytic virus from patient
immune systemimmune system
 (Oxford University)(Oxford University)

 Polymer-coated Adeno VirusPolymer-coated Adeno Virus
 Protects the oncolytic virus from patientProtects the oncolytic virus from patient
immune systemimmune system
 (Oxford University)(Oxford University)
 Heating bone cancer to fever temperatureHeating bone cancer to fever temperature
 Stops production of protective proteinStops production of protective protein
 Oncolytic virus has higher success rateOncolytic virus has higher success rate
 (University of Southern California, San(University of Southern California, San
Francisco)Francisco)

 Smallpox virusSmallpox virus
modified to kill cancermodified to kill cancer
cells and alsocells and also
stimulate productionstimulate production
of white blood cellsof white blood cells
which weaken cancerwhich weaken cancer
 (Stanford University)(Stanford University)

Benefits and Hope for the FutureBenefits and Hope for the Future
 Fewer side effects than other treatmentsFewer side effects than other treatments

 Fewer treatments requiredFewer treatments required
 The virus increases and continues “dosage”The virus increases and continues “dosage”
because it replicates itselfbecause it replicates itself

 Fewer treatments requiredThe virusFewer treatments requiredThe virus
increases and continues “dosage”increases and continues “dosage”
 Treating previously incurable cancersTreating previously incurable cancers

 Fewer treatments requiredFewer treatments required
 The virus increases and continues “dosage”The virus increases and continues “dosage”
 Treating previously incurable cancersTreating previously incurable cancers
 Greater success rate, survival rateGreater success rate, survival rate

SourcesSources
 ""Chemo drug helps cancer-killing virus.Chemo drug helps cancer-killing virus. "" UPIUPI NewsTrackNewsTrack.. (August(August
29, 2006): NA.29, 2006): NA. General OneFileGeneral OneFile. Gale. Washtenaw Community. Gale. Washtenaw Community
College. 17 Jan. 2008College. 17 Jan. 2008
 ""
Mayo Clinic Cancer Center -- Harnessing the Measles Virus to Attack CanMayo Clinic Cancer Center -- Harnessing the Measles Virus to Attack Can
GlioblastomaGlioblastoma MultiformeMultiforme, Other Deadly Cancers., Other Deadly Cancers. ""
The America's Intelligence WireThe America's Intelligence Wire.. (Oct 30, 2006): NA.(Oct 30, 2006): NA. GeneralGeneral
OneFileOneFile. Gale. Washtenaw Community College. 17 Jan. 2008. Gale. Washtenaw Community College. 17 Jan. 2008
 ""
Researchers Find New Cancer-Fighting Virus That Kills Invasive Brain CaResearchers Find New Cancer-Fighting Virus That Kills Invasive Brain Ca
"" CNW GroupCNW Group.. (Oct 31, 2006): NA.(Oct 31, 2006): NA. GeneralGeneral
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SourcesSources
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Virus attack on cancer: heat makes neglected technology work better.Virus attack on cancer: heat makes neglected technology work better. ""
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 ""BIOTECHNOLOGY Progress in MagneticBIOTECHNOLOGY Progress in Magnetic NanoparticleNanoparticle Cancer Therapy.Cancer Therapy. ""
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 ""Drug delivery.Drug delivery. "" Medical Device TechnologyMedical Device Technology.. 17.5 (June17.5 (June
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SourcesSources
 Kasuya, H, Takeda S, Nomoto S., Nakao A. “The Potential ofKasuya, H, Takeda S, Nomoto S., Nakao A. “The Potential of
Oncolytic Virus Therapy for Pancreatic Cancer. Retrieved April 15,Oncolytic Virus Therapy for Pancreatic Cancer. Retrieved April 15,
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Cancer, Developing Novel Gene-Based Approaches” Mayo ClinicCancer, Developing Novel Gene-Based Approaches” Mayo Clinic
Research, Retrieved April 15, 2008 fromResearch, Retrieved April 15, 2008 from
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rogram/overview.cfmrogram/overview.cfm
 The Measles Virus Tamed and Trained, Virotherapy:The Measles Virus Tamed and Trained, Virotherapy:
Reprogramming the Measles Virus to Attack Cancer Cells.Reprogramming the Measles Virus to Attack Cancer Cells.
Retrieved April 15, 2008 fromRetrieved April 15, 2008 from
http://discoverysedge.mayo.edu/measles/index.cfmhttp://discoverysedge.mayo.edu/measles/index.cfm
 Cancer-killing Virus Modified to Deliver a One-Two Punch,Cancer-killing Virus Modified to Deliver a One-Two Punch,
http://www.wired.com/medtech/genetics/news/2007/10/cancer_virushttp://www.wired.com/medtech/genetics/news/2007/10/cancer_virus

SourcesSources
 Genetically Engineered Viruses Set to Fight CancerGenetically Engineered Viruses Set to Fight Cancer
http://www.scienceagogo.com/news/20040416225902dahttp://www.scienceagogo.com/news/20040416225902da
ta_trunc_sys.shtmlta_trunc_sys.shtml
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 ““Measles Virus to Kill Multiple Myeloma” Retrieved AprilMeasles Virus to Kill Multiple Myeloma” Retrieved April
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archives/infectious-disease-news/June-20-2007.htmlarchives/infectious-disease-news/June-20-2007.html

PresentationPresentation
 Presented April 17, 2008Presented April 17, 2008
 Katherine SawyerKatherine Sawyer
 Biology 103Biology 103
 Washtenaw Community CollegeWashtenaw Community College
 (Ann Arbor, Michigan)(Ann Arbor, Michigan)
 Prof. Ross StrayerProf. Ross Strayer

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