Immunotherapy and cancer I Flashcards
why target the immune system?
Ehrlich stated that;
- early tumors never become apparent because they are destroyed by the immune system
examples of some immune modulators
- Coley’s toxins
- Cytokines
- Pattern recognition receptor agonists
- HSP
- Ab therapy
- Inflammation
what is Coley’s toxin?
a therapy developed after it was observed that some cancer patients experienced spontaneous remission after developing bacterial infections.
what does Coley’s toxin contain?
originally, streptococcus pyogenes and serratia marcesens ; heat killed and injected into cancer patients.
what is the idea behind Coley’s toxin?
immune system would be activated by the bacteria which would in turn attack the cancer cells
what is BCG?
bacillus calmette-guerin
- vaccine for TB
- good immunological adjuvant
- stimulaes the innate immune system
- used in bladded cancer
MOA of BCG
DC activation, direct NK activation, bystander T cell activation
Cytokines; interferons
- Type I interferon
- produced by virally infected cells
- viral detection pathways within most cells
- upregulates MHC class I, tumors antigens and adhesion molecules
- activates T-cells, B cells and DC
- used successfully in metastatic melanoma
- nasty flu like side effects
what does DC refer to?
dendritic cells; immune cells , APCs
interleukins
- T cell growth factor
- success in RCC and melanoma
- toxicity
- LAK cells, PBMC treated with IL2 and reinfused into patients
what is GM-CSF?
granulocyte macrophage colony stimulating factor
what is the function of GM-CSF?
cytokine that promotes myeloid cell development and maturation, and dendritic cell differentiation and survival in vitro
success rate of cytokine therapy
- interferons; 10-20%
- IL2; 10-20%
- IL2 + interferons; 40%
- GMCSF; ?
- GMCSF + IL2; 20%
pattern recognition
- intra and extra cellular sensors pathogens associated molecular patterns (PAMPs)
- conserved between species
4 families of pattern recognition
- Toll-like receptors
- Nucelotide-binding oligomerisation domain (NOD_-like receptors
- Retinoic acid inducible gene (RIG)- like receptors
- DNA sensors
pattern recognition receptors ; PRR
- originally though of as sensors for infection but more recently receptors for endogenous ligands
- Danger Associated Molecular Patterns (DAMPs)
- cell injury, stress or cell death