cancer immunotherapy - northwestern university€¦ · how does immunotherapy work? •stimulate a...
Post on 08-Jun-2020
0 Views
Preview:
TRANSCRIPT
CancerImmunotherapy
Presentedto:CancerConnectionsPresentedon:March3,2018Presentedby:JeffreySosman,MD&AparnaKalyan,MBBS
WhatisCancerImmunotherapy?
• Treatmentthatusescertainpartsofaperson’simmunesystem tofightdiseasessuchascancer.
Immunotherapy=Tcellkillsacancercell
2
HowDoesImmunotherapyWork?
• Stimulateaperson’simmunesystemtoworkharderorsmartertoattackcancercells
• Giveapersonimmunesystemcomponents,suchasman-madeimmunesystemproteins
-AmericanCancerSociety
3
VariousClassesofImmunotherapeuticAgents
4
Tumor-DerivedImmuneSuppression
5
WeinerLM.NEngl JMed 2008
ImmunosuppressiveCytokinesTGF-ßIL-4IL-6IL-10
AntigenDownregulationClassIMHClossintumor
cells
Treg
MDSC
Granulocyte
ImmunosuppressiveCellsTumorImmunosuppressiveMolecules(PD-L1)
ImmunosuppressiveEnzymeActivity
Indoleamine 2,3Dioxygenase(IDO)
PositiveandNegativeSignalsRegulateT-CellActivation
6
“Driving”anImmuneResponse
7
T-cell receptor: Antigen-MHC
CD28: B7
CTLA-4: B7
Vaccine?
IpilimumabAugmentstheActivationoftheT-Cell
8
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
10
AdoptiveCellularTherapy
11
AntibodiesCanBeModifiedtoBeMoreHumanand
DeliverAgentstoTumorSites
12
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
13
Questions?AsktheExperts!
top related