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Title: Cancer immunotherapy
Description: Notes on the different immunotherapies that are used in cancer cases. Especially useful for students studying third year medicine, biomedical science, immunology, or oncology. They include CAR T cell therapy, and others; both antigen specific and non-specific. It also covers tumour associated and specific antigens, along with basic and in depth definitions.
Description: Notes on the different immunotherapies that are used in cancer cases. Especially useful for students studying third year medicine, biomedical science, immunology, or oncology. They include CAR T cell therapy, and others; both antigen specific and non-specific. It also covers tumour associated and specific antigens, along with basic and in depth definitions.
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Cancer immunotherapy
Cancer- disease from the uncontrolled proliferation and spread (metastases) of clones of
transformed cells
...
Immunotherapy for cancer relies on augmenting tumour antigenicity (ability to induce
immune response)
...
Direct cytotoxic treatment
...
Tumour specific antibodies in cancer patients
...
Tumour antigens- any protein produced in a tumour cell that has an abnormal structure due
to mutation can act as a tumour antigen
...
EGFR, VEGF, Alphafetoprotein, CA125, CEA
Tumour antigen picked up by a dendritic cell- presentation and attract CD8 and 4, etc
...
Tumour escape from immune responsesDown regulation of MHC1- less production of b2globin
...
High rate of mitosis, genetic instability, antigenic modulation
...
Dysregulated expression of adhesion and costimulatory molecules- evidence that
tumour-infiltrating DC are MHC2 but lack expression of CD80 and CD86
...
Principles of immunotherapy
Non-specific immunotherapy (doesn’t target a specific antigen)- BCG, cytokine treatment,
IFN alpha-routinely used in treatment of RCC
Specific immunotherapy (targets specific antigen)- cancer vaccines, antibody treatmentrituximab, herceptin, bevacizumab, cetuximab
...
BCG FDA approval 1989 for CIS or failure of primary
treatment
...
Side effects- cystitis-42%, haematuria- 35%
...
No dose-response effect except
toxicity- antiviral, antiproliferative, immunomodulatory
...
Stage 4 mainly evaluated, median survival 6-9m
...
8months
...
● Vaccination- highly effective against cancers induced by viral infections eg
...
Therapeutic vaccines a lot less effective due to immunological tolerance
...
Has been some relative success
...
Targeting ErbB2 in some vaccines, including oral salmonella
ones
...
mechanism of killing- cell surface receptor agonist and antagonist activity leads to
apoptosis, inhibit signalling, reduce proliferation
...
Vascular and stromal ablation- stromal cell inhibition
...
Angiogenesis is involved throughout tumour formation, growth,
and metastasis
...
Transport has to be
very quick and constantly in sterile environment- can cuase complications in the
treatment
...
People lived twice as long with this vaccine
...
Types- LAK cells- from blood lymphocyte-activated killer cells mainly NK cells (few
CTLs) use with melanocytes
...
CAR-T cell- adoptive transfer of genetically modified T cells
...
advanced follicular lymphoma-dramatic regression
...
T cells with a CAR protein on their surface bind to their
target and no longer require antigen-presentation by dendritic cells to become active
...
Lots of potential
targets are being investigated in trials
...
Sticking points: lack of trafficking to the tumour; abnormal blood vessels
and physical barriers impede CAR T cell movement; immune-suppressing
microenvironment; lack of specificity for tumour cells, hence severe side effects
...
Another molecule is PD1 (t cell) and PDL1 (tumour cell), they
are targeted antibodies- increase the activity of CTLs; reduce the activity of Tregs;
reverse the exhaustion of CTLS; increase activity of B cells and NK cells; are
probably equivalent to one another in terms of their efficacy
...
Checkpoint
inhibitors can be used alone and in combination: high PDL1 expressionimmunotherapy monotherapy may be sufficient; PDL1 expression is low or absentimmunotherapy combination- can be used with chemo or radiotherapy, or targeted
therapy to enhance immunogenicity or create a pathway-specific interaction
...
Has to be treated by high doses of steroids which override the
over-action of the immune system, otherwise people will die
...
50% of patients ended up in hospital because
of this drug, yet it is effective
...
Title: Cancer immunotherapy
Description: Notes on the different immunotherapies that are used in cancer cases. Especially useful for students studying third year medicine, biomedical science, immunology, or oncology. They include CAR T cell therapy, and others; both antigen specific and non-specific. It also covers tumour associated and specific antigens, along with basic and in depth definitions.
Description: Notes on the different immunotherapies that are used in cancer cases. Especially useful for students studying third year medicine, biomedical science, immunology, or oncology. They include CAR T cell therapy, and others; both antigen specific and non-specific. It also covers tumour associated and specific antigens, along with basic and in depth definitions.