Oncolytic Virus Therapy

Oncolytic Viral TherapyOncolytic Viral TherapyPresented 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 cell Unusual cell

growthgrowth Caused by Caused by

genetic mutationgenetic mutation Usually in form Usually in form

of tumorof tumor

Onco = CancerOnco = Cancer Cancer ……Cancer ……

Unusual cell growthUnusual cell growth Caused by genetic mutationCaused by genetic mutation Usually in form of tumorUsually in form of tumor

Blocks immune Blocks immune system with system with proteinsproteins

Takes Takes resources from resources from healthy cellshealthy cells

Onco = CancerOnco = Cancer Cancer ……Cancer ……

Unusual cell growthUnusual cell growth Caused by genetic Caused by genetic

mutationmutation Usually in form of tumorUsually in form of tumor Blocks immune system Blocks immune system

with proteinswith proteins Takes resources from Takes resources from

healthy cellshealthy cells

Can occur in Can occur in almost any almost any tissuetissue

Cancer TreatmentsCancer Treatments

SurgerySurgery Remove tumor Remove tumor Success if all of tumor is removed, but many Success if all of tumor is removed, but many

cancers metastasize (break and spread) or cancers metastasize (break and spread) or have irregular shapes difficult to removehave irregular shapes difficult to remove

Risk associated with any invasive surgery Risk 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 kills Often severe side effects because it also kills

some healthy cells some healthy cells Effective but side effects significant (nausea, Effective but side effects significant (nausea,

fatigue, immune weakness)fatigue, immune weakness)


RadiationRadiation Radiation aimed at tumor to kill the tumor Radiation aimed at tumor to kill the tumor

cellscells

Side effects severe, significant damage to Side effects severe, significant damage to surrounding tissuesurrounding tissue

Effective in reducing tumorEffective in reducing tumor


NanotechnologyNanotechnology Use carbon or other molecule to carry drug or Use carbon or other molecule to carry drug or

radiation to the tumorradiation to the tumor Use shells of cells to carry drugs Use shells of cells to carry drugs Attach drugs to molecules that can fit through Attach drugs to molecules that can fit through

wide cancer blood vessels that healthy cells wide cancer blood vessels that healthy cells don’t havedon’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 Re-program cancer cells’ DNA to make it die Re-program cancer cells’ DNA to make it die

young.young.


Oncolytic Viral TherapyOncolytic Viral Therapy Genetically modifying a virus so that it kills Genetically 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 like Disease 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, no beneficial viruses (always Unlike bacteria, no beneficial viruses (always kills its host)kills its host)

Virus: StructureVirus: Structure

Protein shell called a Protein shell called a capsid contains DNAcapsid contains DNA

Arrangement of one Arrangement of one or more protein fibers or more protein fibers for bonding with host for bonding with host cellcell

Virus: StructureVirus: Structure

Virus: ReproductionVirus: Reproduction

Attaches to host cell with spikes or Attaches 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 building Uses the cell’s DNA as building blocksblocks for its new for 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 successful Choose a resilient virus that is successful in human bodyin human body MeaslesMeasles HerpesHerpes Adeno virus (common cold)Adeno virus (common cold) Influenza virusInfluenza virus


Choose a resilient virus that is successful Choose a resilient virus that is successful in the human bodyin the human body



Splice DNA into virus DNA that codes for a Splice DNA into virus DNA that codes for a protein that bonds well and is attracted to protein that bonds well and is attracted to tumor’s proteintumor’s protein



Splice DNA into virus DNA that codes for a Splice DNA into virus DNA that codes for a protein that bonds well and is attracted to protein 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

Oncolytic Viral Therapy: Oncolytic Viral Therapy: ChallengesChallenges

Main challenge is patient’s own immune Main challenge is patient’s own immune system killing the virus before the virus system killing the virus before the virus can kill the cancer. can kill the 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: TrialsOncolytic Viral Therapy: Trials

Measles VirusMeasles Virus Most successful trial Most successful trial Brain cancer –high Brain cancer –high

success rate Mayo success rate Mayo Clinic)Clinic)

Multiple myeloma --Multiple myeloma --previously incurable previously incurable bone cancer (Mayo bone cancer (Mayo Clinic)Clinic)


Seneca Valley Seneca Valley VirusVirus Developed by Developed by

Neoptrix Neoptrix Successful at Successful at

destroying small destroying small cell lung cancer cell lung cancer


Adeno Virus (cold Adeno Virus (cold virus)virus) Designed to kill cells Designed to kill cells

with common mutation with common mutation of colon cancer of colon cancer (unidentified research (unidentified research group)group)

Successful with Successful with breast, liver, skin breast, liver, skin cancers (University of cancers (University of Birmingham)Birmingham)


Herpes VirusHerpes Virus Variety of tumors Variety of tumors

(Baylor University in (Baylor University in San Diego with San Diego with Immusol in China)Immusol in China)

50% success rate with 50% success rate with pancreatic cancer pancreatic cancer previously a nearly previously a nearly untreatable cancer untreatable cancer (Nagoya University, (Nagoya University, Japan)Japan)

Oncolytic Viral Therapy: Oncolytic Viral Therapy: Specialized TrialsSpecialized Trials

Measles VirusMeasles Virus . Fusogenic . Fusogenic

Membrane Membrane GlycoproteinsGlycoproteins

(FMG)(FMG) Causes cancer Causes cancer

cells to fuse with cells to fuse with each other and die each other and die

(Mayo Clinic)(Mayo Clinic)

Oncolytic Viral Therapy: Oncolytic Viral Therapy: SpecializedTrialsSpecializedTrials

Intravenous VS Virus Intravenous VS Virus First trial of intravenous oncolytic viral First 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 Virus Polymer-coated Adeno Virus Protects the oncolytic virus from patient Protects the oncolytic virus from patient

immune systemimmune system (Oxford University)(Oxford University)


Polymer-coated Adeno Virus Polymer-coated Adeno Virus Protects the oncolytic virus from patient Protects 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 virus Smallpox virus modified to kill cancer modified to kill cancer cells and also cells and also stimulate production stimulate production of white blood cells of white blood cells which weaken cancerwhich weaken cancer

(Stanford University)(Stanford University)

Oncolytic Viral Therapy: Oncolytic Viral Therapy: Benefits and Hope for the FutureBenefits and Hope for the Future

Fewer side effects than other treatmentsFewer side effects than other treatments


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 side effects than other treatmentsFewer side effects than other treatments Fewer treatments requiredThe virus Fewer treatments requiredThe virus

increases and continues “dosage” increases and continues “dosage” because it replicates itselfbecause it replicates itself

Treating previously incurable cancersTreating previously incurable cancers


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

Treating previously incurable cancersTreating previously incurable cancers Greater success rate, survival rateGreater success rate, survival rate

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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

Oncolytic Virus Therapy

Technology

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