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Samenvatting WEEK 5-10 (Deel 2) Immunotherapie

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Complete, duidelijke, overzichtelijke samenvatting van het tweede deel van de cursus Immunotherapie. Het gaat vooral over nieuwe ontwikkelingen in toepassing van immunotherapie tegen kanker.

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  • June 23, 2019
  • 41
  • 2018/2019
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Samenvatting - Immunotherapie

Inhoudsopgave
HC: Hematologische maligniteiten.......................................................................................................................2
HC: Inleiding oncologie.........................................................................................................................................4
HC: Oncologie, immunotherapie..........................................................................................................................5
WG: Antitumor antistoffen...................................................................................................................................6
Groep 1: Transtuzumab/Rituximab.................................................................................................................8
Groep 2 = IgA...................................................................................................................................................8
Groep 3 = anti-CTLA-4......................................................................................................................................9
Groep 4 = CD47/SIRPa.....................................................................................................................................9

Week 6........................................................................................................................................................ 11
HC: Checkpoint inhibitors...................................................................................................................................11
HC: Virus-induced tumors...................................................................................................................................14
HC: Adoptieve immunotherapie bij virus gemedieerde maligniteiten...............................................................16

Week 7........................................................................................................................................................ 18
HC: Cellulaire immuun therapieën.....................................................................................................................18
HC: Tumor immunotherapie bij innate immuun cellen......................................................................................19
HC: Antilichaambehandeling van maligne lymfomen........................................................................................21
WG: Effectormechanismen van cellulaire IT......................................................................................................23
Death cel receptor.........................................................................................................................................24
Granule exocytosis pathway..........................................................................................................................24
HC: Dendritische cellen in immunotherapie.......................................................................................................25
WG: DC-vaccins..................................................................................................................................................28

Week 8........................................................................................................................................................ 29
HC: HLA-systeem, donor selectie SCT, GvHD en GvT..........................................................................................29
HC: Hematologische maligniteiten: diagnostiek/detectie MRD........................................................................31
HC: TEG001: from bench to bedside...................................................................................................................32
WG: Minisymposium: immune evasion..............................................................................................................33
MDSC.............................................................................................................................................................35
Treg................................................................................................................................................................35
Dendritische cel.............................................................................................................................................35
Macrofaag......................................................................................................................................................36

Week 9........................................................................................................................................................ 38
HC: Immunogentherapie....................................................................................................................................38
WG: HLA in transplantaties................................................................................................................................40
Groep 1: donor selectie in HSCT....................................................................................................................40
Groep 2: transplantatie met navelstrengbloed (AML)..................................................................................40
Groep 3: anti-HLA antistoffen........................................................................................................................40
Groep 4: HSCT van een teruggevallen patiënt..............................................................................................41
Week 5

1

,HC: Hematologische maligniteiten

Belangrijkste hematologische maligniteiten
- Acute leukemie
o Proliferatie van blasten met uitrijpingsstop: ophoping ongedifferentieerde cellen
- Myelodysplasie = MDS
o Dysplasie, gestoorden differentiatie en verhoogde apoptose --> cytopenie
- Myeloproliferatieve neoplasmata = MPN
o Activatie receptor --> verhoogde aanmaak (differentiatie is normaal)
- Lymfatische maligniteiten
Kenmerkend zijn de genetische mutaties die algemeen, danwel specifiek (voor het fenotype) kunnen
zijn.

Clonale evolutie: genetische verandering in de tijd.




Beenmergonderzoek kan via:
- Cristabiopt
- Crista aspiraat
- Sternum aspiraat

Flowcytometrie differentieer je eiwitten en kan je markers vinden.
Cytogenetisch: chromosomen structuur
Moleculair: specifieke DNA veranderingen


Acuut leukemie:
> >20% blasten beenmerg, verdringing normaal beenmerg

2

, > Verschillende types
MDS (=myeloide dysplasie)
> Abnormaal en ineffectieve rijping
> Hoge cellen in beenmerg en verhoogde apoptose
> Dysplasie + cytopenie in bloed
> <20% blasten in beenmerg \
MPN (=myeloproliferatieve neoplasma)
> Verhoogde aanmaak, rijping normaal

Dasatinib: remt Bcr-Abl (functie normal is proliferatie)

Myelofibrose = firbosering beenmerg
- Anemie, leuko-erytroblastose, splenomegalie
- Vaak mutaties in JAK2, MPL, calreticuline
- Behandeling: transfusie, JAK2 remming = ruxolitinib

Hodgkin lymfoom --> Reed-sternberg cel

MM: groei plasmacellen en activatie osteoclasten in het beenmerg
- M-proteïne
- Kliniek: osteolyse, hypercalcium en fracturen

Immuunsysteem probeert afwijkende cellen op te ruimen
> Maligniteit: omzeiling immuunsysteem door tolerantie te induceren met Treg of upregulatie
van checkpoint inhibitors.

SCT
1. Autoloog
a. Hoge dosis chemo
b. Beenmerg of perifere bloedstamcellen van te voren verzameld en tijdelijk ingevroren
worden ingespoten en zorgen voor herstel van de beenmerg functie.
2. Allogeen
a. Nieuwe stemcellen
b. Donor T-cellen ruimen maligne en normale cellen op
c. Let op! GvHD




3

, HC: Inleiding oncologie

Behandeling kanker
1. Locoregionaal
a. Operatie
b. Bestraling
2. Systemisch
a. Anti hormonaal
b. Chemotherapie: oraal of i.v. Nadelen zijn bijwerkingen en resistentie
c. Targeted
d. Immuuntherapie

(Neo)adjuvant = in combinatie met operatie/bestraling
- Neo adjuvant krijg je eerst chemo en daarna operatie/bestraling
- Adjuvant krijg je eerst operatie/bestraling en daarna chemo
Palliatief = als geen genezing mogelijk meer is




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