CanImmun Flashcards
What are the 3 phases of immunoediting?
→Elimination
→Equilibrium
→Escape
What danger signals are expressed on tumour cells?
→MICA an ULBP
→RAE1
What are MICA/B recognised by?
→gamma delta cells which express NKG receptors
Which innate cells are involved in the elimination phase of immunoediting?
→NKs →NKTs →Macs →DCs →Tumour specific CD4+ and CD8+ T cells
What signals lead to tumour death in elimination?
→INF-gamma
→chemokines
How do tumour cells hide from immune system?
→modulate MICA/B
How does BCG act as a cancer immunotherapy?
→Stimulates the innate immune system TLRs
What cancers is BCG used for?
→bladder cancer- intravessicular injection
What is BCG vaccine originally for?
→TB
Which pathogens produce Type 1 interferon alpha and beta?
→virus
How does Type 1 inteferon work as cancer immunotherapy?
→Upregulates MHC Class 1, increased expression tumour antigens and adhesion molecules
→Activates T cells, B cells and DC
What are the side effects of interferon cancer use?
→flu-like symptoms
How is interleukin-2 used for cancer therapy?
→T cell growth factor
→Success in RCC(renal cell carcinoma) and melanoma
How is the toxicity of interleukin cancer use mediated?
→LAK cells, PBMC treated with IL-2 and re-infused into patients
How is GM-CSF used in cancer therapy?
→stimulates APC
→benefit if used in conjunction with IL-2
How are Abs used in cancer therapy?
→direct ymour cell killing →activate phagocytosis, complement, and ADCC →vascular and stomal cell ablation →anti-CTLA4 →cross presentation and Tcell actiavtion
How does Trastuzumab work in breast cancers?
→targets ERBB2 (human epidermal growth factor) on breast cancer cells.
→Blocks ERBB2 signalling and allows targeting of ADCC
How does Bevacizumab(Avastin) work as cancer therapy?
→targets VEGF and blocks signalling
Give examples of drugs that induce apoptosis
→Rituximab: anti-CD20
→Alemtuzumab (Campath): anti CD52
→Target all Bcells
What cancer is anti-CTLA4 used for?
→metastatic melanoma
What are some delivery cancer therapy methods?
→90Yttrium-labelled ibritumomab tiuxetan. Antibody to CD20 delivering radiotherapy to follicular B-cell NHL
→Brentuximab vedotin: antibody to CD30 delivering toxin (Aurostatin) to CD30+ B cells in NHL
→Ontak: IL-2 delivering diphtheria toxin in T cell lymphoma
What are some checkpoint inhibition therapies?
→Blockade of effector cell death
→Antibody against PD-1 (programmed cell death protein 1)
What are some cell based therapies for cancer?
→LAK →NK-T cells →gd T cells →DC →TIL →CAR
What are LAK cells?
→Lymphokine Activated Killers
→NK, NKT and T cells (CD25+)
→Predominantly NK cells
→Can target NK resistant tumour cells
What markers are NK cells positive for?
→CD3- CD56+
→ subsets CD56 bright and CD56 dim
→CD16+/CD16- (FcRIII)
Where are NK cells predominantly found?
→blood
→BM
→liver
→spleen
What is involved in NK-T immunotherapy?
→a-galactosyl ceramide
What do gamma-delta Tcells respond to?
→MICA and MICB expressed on stressed cells
→small organic molecules secreted by bacteria: eg HMBPP ((E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate) from mycobacteria
→May not need normal antigen presentation mechanisms
→Single cell type most favourably good outcome
What cells does therapeutic vaccination use?
→APCs
What are the principles of DC vaccination for cancer therapy?
→DCs are extracted from patients and then exposed to either digested tumor peptides or messenger RNA from the patient’s autologous tumor
→ The DCs are then transfused back into the patient, primed and ready to activate immune responses
What are TILs?
→recognize and kill cancer cells
What is adoptive cellular therapy?
→Tumour biopsy
→In vitro polyclonal stimulation (IL-2 and anti-CD3 antibody) to expand and then put back into patient
→Best results when patients are pre-treated with peripheral lymphodepletion regimen of total body irradiation
What are the disadvantages of TIL adoptive cell therapy?
→Need enough tumour to generate sufficient CTLs
→TILs may be refractory to stimulation (about 30%)
→Time consuming and labour intensive – requires infrastructure.
→Culture time may be too long for patients
→Culture time MAY influence quality of T cells- the longer Tcells are maintained in culture, the less specific they become.
→High failure rate of culture.
What is ACT using peripheral blood Tcells?
→Clonal expansion against a known antigen
→easy availability of large numbers of T cells
Peripheral blood contains many precursors with TAA reactivity
What is high affinity TCR transduction for cancer therapy?
→Alpha and beta chains of TCR are engineered into a retroviral vector.
→Patient’s CD8+ T cells from peripheral blood are removed and transduced with TCR-virus.
→Adoptive transfer back into patients
→Engineering Tcell specific to tumour antigen
What is CART?
→Similar in nature to TCR transgenics, but NOT MHC restricted
→CARs are designed to allow the T cells to attach to specific proteins on the surface of the cancer cells
