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CancerImmunotherapy
Presentedto:CancerConnectionsPresentedon:March3,2018Presentedby:JeffreySosman,MD&AparnaKalyan,MBBS
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WhatisCancerImmunotherapy?
• Treatmentthatusescertainpartsofaperson’simmunesystem tofightdiseasessuchascancer.
Immunotherapy=Tcellkillsacancercell
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HowDoesImmunotherapyWork?
• Stimulateaperson’simmunesystemtoworkharderorsmartertoattackcancercells
• Giveapersonimmunesystemcomponents,suchasman-madeimmunesystemproteins
-AmericanCancerSociety
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VariousClassesofImmunotherapeuticAgents
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Tumor-DerivedImmuneSuppression
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WeinerLM.NEngl JMed 2008
ImmunosuppressiveCytokinesTGF-ßIL-4IL-6IL-10
AntigenDownregulationClassIMHClossintumor
cells
Treg
MDSC
Granulocyte
ImmunosuppressiveCellsTumorImmunosuppressiveMolecules(PD-L1)
ImmunosuppressiveEnzymeActivity
Indoleamine 2,3Dioxygenase(IDO)
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PositiveandNegativeSignalsRegulateT-CellActivation
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“Driving”anImmuneResponse
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T-cell receptor: Antigen-MHC
CD28: B7
CTLA-4: B7
Vaccine?
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IpilimumabAugmentstheActivationoftheT-Cell
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CD80/CD86
T-cell inhibition
CTLA-4
CD28
T-cell
APC
TCR
HLA
T-cell activation
CD28TCR
HLA
T-cell
APC
CD80/CD86
T-cell remains active
Ipilimumabprevents
CTLA-4 fromInhibiting T cell
activation
T-cell
APC
CTLA-4
CD80/CD86
TCR
HLA
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InhibitedT cell
Tumor cellDeath
Tumor cell
MHC + tumor
antigen
Cytokines, cytolytic molecules
PD-L1
Nivolumab
PD-L2
Nivolumab
How do Anti-PD-1/PD-L1 Antibodies work?
Tumor Microenvironment 9
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TumorsResponsiveto(Approvedfor)PD1/PD-L1Blockade
• Melanoma
• RCC
• NSCLC
• Bladder(Urothelial)
• Head&NeckSquamousCellCancer
• MerkelCell
• Hodgkin’sDisease
• Gastro-Esophageal
• Hepatocellular
• MismatchRepairDeficientTumors
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AdoptiveCellularTherapy
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AntibodiesCanBeModifiedtoBeMoreHumanand
DeliverAgentstoTumorSites
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Antibodies can act to target cytotoxand toic drugs, radioisotopes,
immune cytokines, and immune effector cells to sites of tumor
Antibodies can be modified from a foreign mouse protein
(antibody) to a completely humanized antibody. This
may decrease their immunogenicity and improve
function.
BITE
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TumorVaccines
1. WholeTumorCellVaccines2. PeptideVaccinesfromtumorassociatedproteins(TAA)3. DNAVaccines– isolatedtumorDNA4. DendriticCell(DC)Vaccinespulsedwithpeptides(TAA)5. DCVaccinesintotumors
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Questions?AsktheExperts!