Immunotherapy Flashcards
each year how many people worldwide are diagnosed with cance
14.1 million
half of .. will get cancer
men
1/3 of … will get cancer
females
immunocompromised individuals are
more susceptible to cancer than the general population
which cytokine is specifically immune-protective against cancer
IL-2
tumour micro-environment is rich in
Tumour infiltrating T-lymphocytes (TILs)
those patients with few TILs are
far more likely to die
non-small cell lung carcinomas are often found to be being fought by
CD8 Cytotoxic T cells
process immune system uses to recognise cancer cells
1) cancer cells will display calreticulin on its plasma membrane
2) this signals for macrophophages to phagocytose the cancer cell
3) macrophage e.g. dendritic cell stimulates naive T cells (e.g. via MHC I and CD8)
4) killer T cell expansion
5) eliminate cancer cell
3 passes of cancer immune surveillance
elimination –> equilibrium –> escape
elimination stage of cancer immune surveillance
innate and dative immune response against active tumour ( B cells and Ig, T cells, Treg, NK cells
equilibrium stage of cancer immune surveillance
tumour is contained by immune system but not completely destroyed
escape stage of cancer immune surveillance
tumour antigen editing vi genomic instability causes immune evasion and tumour micro-environment becomes immunosuppressive
tumour micro-environment is rich in immune suppressive signals
- high levels of suppressive cytokines
Initiation of T tags (inhibit DCs) - low MHC expression on tumour cells
- high expression of immune checkpoint proteins on T cells
- high expression of immune checkpoint protein inhibitors on tumour cells
most tumur antigens are recognised by
adaptive immunity as self antigens
T cell activation involves
positive and negative signals flowing in both direction
types of cancer treamtent
surgery, radiation, chemotherapy, immunotherapy, targeted therapy, hormone therapy etc
immunotherapy is
specific , powerful, universal, memory
immunotherapy is not a new idea0 however technique was limited until
advent of hybridoma technology
production of monoclonal antibodies via hybridoma technology
renewed interest int targeting human tumours for diagnosis and therapy
detection of tumour-associated antigens offers an attractive target for
radioisotopes or other toxic substances carried to tumours by mAbs for treatment or imaging purposes
examples of how the immune system can be harnessed to target cancer
- passive vaccination
- activate vaccination
- immune system modulators
- immune checkpoint modulation
- immune cell therapy
passive vaccination
therapeutic monoclonal antibodies
active vaccination
e.g. HPV vaccines and cervical cancer
immune system modulators
e..g IL-2 activates CD8 T cell
therapeutic monoclonal antibodies
carry cytotoxic agents to tumour
induces complement-mediated lysis or ADCC of tumour cells
block activity of tumour-specific proteins
rituximab- therapeutic monoclonal antibodies and Hodjkins Non-lymphoma
- induce complement -mediated lysis or ADCC of tumour cell
herceptin- therapeutic monoclonal antibodies and breast cancer
block activity of tumour-specific proteins
3 ways of using therapeutic monoclonal antibodies
1) naked Mob
2) immunoconjugates
3) multistep targeting
Naked MAb are used to
induce ADCC and CDC in tumour cells
example of immunoconjugates
Immunocytokinfe, radioimmunocongjugate, immunotoxin, celllular immunocongjugates (killer cell), immunoliposome
Antibody-guided chemotherapies
use of radioisotopes, drugs and tons conjugated to monoclonal antibodies
chemotherapeutic agents used for antibody -guided therapy of cancer
Cisplatin , emthotexate etc
Toxins used for antibody-guided theory of cancer
Rick, abrin, diphtheria
Non-hodjkins lymphoma
NHL is a malignant growth of B cells that results in tumours in lymph nodes and throughout the body
- no cure for most paitents- only 60% of patients treated with radiation and chemotherapy are still alive after 5 years
NHL and chemotherpay
Fludarabine- many side effects e.g. vomiting, nausea, ovaries stop producing hormones
- develops diabetes, severe folic acid deficiency, anaemia
- after 18 months chest scan reveals NHL is back
what is used to treat NHL
a chimeric therapeutic monoclonal antibody called Rituximab
rituximab is the
first monoclonal antibody treatment approved for cancer
how does Rituximab work
a chimeric human-mouse mAB targeted against CD20 - an antigen present on surface of neoplastic B cells
- lyses cells using human complement or ADCC
NHL immunotherapy
- much more effective than chemotherapy
- no toxicity associated with the treatment
breast cancer
v common cancer (1 in 9 women)
- two ends have been identified BRCA1 and BRCA2
women with mutation in BRCA2 tumour suppressor gene
have greatly elevated risk of developing breast and ovarian cancers
which antigen to breast cancer cells express
HER
- breast cancer cells divide and grow when he protein Human Epidermal GF attaches itself to HER2
what is used to treat breast cancer
humanised monoclonal antibody Herceptin
herceptin is mainly used to treat women
with advanced breast cancer and is given in combination with chemotherapy drugs such as Taxol
Alzheimers disease: which antibody is a neuroprotector
Solanezumab
Solanezumab …
mAb binds to amyloid0B peptides
- binding to central epitope KLVFFAD with pciomolar affinity
- epitope s enucleation site for AB polymerisation
- oligomers of AB toxic to neurones
which antibody used in Rheumatoid arthiritics
Toxilizumab
Toxilizumab
Humanised anti-human IL-6R receptor antibody
- blocks binding of IL-6
