novel cancer therapies 1 Flashcards
what are examples of immunotherapy approaches
targeted antibodies, adaptive cellular therapy, cytokines
what is Coley’s toxin
the first attempt at immunotherapy and hyperthermia and cancer
what do therapeutic vaccines contain
modified tumour cells, tumour-associated antigens, dendritic cells and oncolytic vaccines
what are the characteristics of germ line antigens
expressed only by tumour cells and adult reproductive tissues
what are the characteristics of differentiated antigens
expressed by tumours and.a limited range of normal tissues
what are the characteristics of over expressed antigens
expressed in normal and tumour cells, expressed too much in tumour
what are the characteristics of viral antigens
expressed only by tumour cells as a result of a viral infection
what are dendritic cells
antigen presenting cells
how can dendritic cells be used for cancer therapy
you can take blood containing monocytes and stimulate them in vitro to become dendritic cells, you can then tweak dendritic cells to give you the response you want
how have dendritic cells been used in prostate cancer
Used with the fusion protein prostatic acid phosphatase PAP → this antigen is present in prostate cancer.
This is coupled to granulocyte Macrophage colony-stimulating factor GM-CSF which stimulates dendritic cells.
You transect the dendritic cells and give it back as a therapy.
what is the function of monoclonal antibodies
induce or promote an immune response
how can monoclonal antibodies be used for cancer therapy? Give an example
Rituximab recognises CD20 Which is highly expressed on B cells and highly expressed on B cell tumours . Rituximab is a very effective therapy when rituximab binds to CD20 on the B cell It induces apoptosis . The problem with this therapy is it kills normal B Cells, If not careful the patient can become immunosuppressed
what are the disadvantages of adaptive T cell therapy
expensive and complex
what is adaptive T cell therapy
Take the effector cell that can destroy cancer that is the T cell and improve It is killing ability by In vitro stimulation. There are 3 ways to do this :
1. tumour infiltrating lymphocytes
2.CART
3.T cells
For all Steps, It Is Important the patient is conditioned.
what is conditioning
purposely making the patient immunosuppressed so engineered T cells will expand in the body
what are the two ways to isolate and modify T cells
- clone a T cell receptor
2. chimeric antigen receptor CAR
what is clone a T cell receptor
cloning a T cell which recognises the cancer antigen and clone it so more T cells can recognise the antigen
what is chimeric antigen receptor CAR
modify the T cell to see a particular target on the surface of a tumour cell and using that very specifically as a target to get the T cell to grow and to become cytotoxic
steps of CAR-T therapy
1. take blood from patient 2- Isolate the T cells 3 . Introduce CAR to T - cells 4- grow millions of cells 5. Infuse back Into the patient on the understandingthat theywill bind to cancer cells and kill them
CAR-T therapy is an important treatment in
leukaemia and lymphoma
how does CAR-T cells work
modify the target on the T cell with CAR so when it comes into contact with the antigen the T cell become cytotoxic
what is an advantage of CART cells
long lasting and keeps patients in remission
what happens at the lymph nodes and the peripheral tissue in immune checkpoint inhibition
lymph nodes: dendritic cells receive an activation signal that helps T cells respond.
Peripheral tissues: can block T cells binding to MHC, PDL1 can switch off PD1 which makes treatment ineffective.
However, monoclonal antibodies can block interactions between PDL1 and PD1 by blocking CTLA-4 on dendritic cell
what distinguishes between a cold and hot tumour
the microenvironment
what is a tumour associated antigen referred to as
neoantigen
why is neoantigen important
people with higher Neo-antigen rates produce better survival rates
neoantigen depends on
- micro immune environment
2. degree of expression of neoantigens within the tumour environment
what is the biggest problem of immune checkpoint inhibition
autoimmunity
