CancerImmunotherapy

Presentedto:CancerConnectionsPresentedon:March3,2018Presentedby:JeffreySosman,MD&AparnaKalyan,MBBS

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)

PositiveandNegativeSignalsRegulateT-CellActivation

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“Driving”anImmuneResponse

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T-cell receptor: Antigen-MHC

CD28: B7

CTLA-4: B7

Vaccine?

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

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

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

TumorVaccines

1. WholeTumorCellVaccines2. PeptideVaccinesfromtumorassociatedproteins(TAA)3. DNAVaccines– isolatedtumorDNA4. DendriticCell(DC)Vaccinespulsedwithpeptides(TAA)5. DCVaccinesintotumors

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