5: Brain Tumors

Question 1

Brain Tumors

Answer 1

Primary Brain Tumor = origin in brain (&stay there)
Secondary Brain Tumors = Metastases in brain, 10x häufiger

Most frequent:
- non-malignant meningioma
Most frequent malignant:
- Glioblastoma

Question 2

Typical clinical scenario:

Answer 2

Patient presents with epilepsy/confusion/focal deficits/cranial pressure
-> imaging
-> surgery/biopsy

Question 3

Etiology: environmental and genetic factors:

Answer 3

• Allergies somehow protective
• Ionizing Radiation as riskfactor
• Cell phones have no effect
• Genetic risks (only 5% of brain tumors)

Question 4

Treatment of glioblastoma

Answer 4

• biopsy/resection
• MRI/CT
• Chemo/Radiotherapy/Chemoradiotherapy
• in intervals: neurological examination and imaging
• repeat surgery, chemo/radiotherapy
  Or
• palliative care

Question 5

Conventional treatments:

Answer 5

Surgery, chemo-, radiotherapy -> survival still very low

Question 6

Targeted Therapy

Answer 6

NTRK gene fusions: neurotrophic tyrosine receptor kinase (NTRK) genes -> in ≤2% of gliomas, very few

Question 7

Immunotherapy

Answer 7

Immunecells can enter brain!

Immunosuppression
Glioblastoma has low mutationrate
-> Immunecheckpoint inhibitors
• CTLA4 in lymphnodes -> so immunecells won‘t attack healthy cells
• PD-1 blocks Antybodies

-> Doesn‘t work!

Question 8

Peptide Vaccination

Answer 8

No effect / doesn‘t work

Question 9

Cytokine based therapy:

Answer 9

• Immunocytokines target tumor-associated ECM proteins
• Immunocytokine is proinflammatory -> binds to tumor -> makes it immunogenic
• Selective tumor targeting in vivo -> Antibodies only in tumor area
• Long-lasting anti-tumor effect in preclinical glioma models
-> survival without retreatment (immune memory)
-> many more T-cells after

Question 10

Adoptive cell therapies with engineered immune cells:

Answer 10

CAR-T-cells (Chimeric Antigen Receptors) -> can target any given tumor antigen
-> allow custom engineering of T-cells

CAR-T-cells against glioblastoma -> very effective in vitro and mouse models

-> Enhancing CAR-T-cell activity

Multifunctional CAR-T-cells against glioblastoma
-> only CAR-T-cells dont help but multifunctional ones with cytokines do

Question 11

Glioblastoma outlook

Answer 11

• Glioblastoma never a single pathway disease: will targeted therapy ever work? -> probably not
• Immunotherapy holds promise, but needs to be better delivered and needs to hit harder
• Combination strategies have huge potential but need to be carefully studied