Immunotherapy 2 Flashcards

1
Q

Mechanism of immune checkpoint protein inhibition

A

1) co-stimulation i CD28 ligation trances T cell activating signs (when presented to MHC on APC)
2) CTLA-4 ligaton on activated T cell down-regulates T cell responses
3) blocking CTLA-4 legation enhances T cell response

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2
Q

when CTLA-4 on T cell binds B7 on APC

A

no cell activation

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3
Q

When anti-CTLA4 mAB blocks CTLA-4 from binding to B7

A

T cell activation

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4
Q

example of an immune checkpoint proteins

A

CTLA4- keeps immune responses in check by preventing overly intense responses that might damage normal cells

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5
Q

first drug used to modulate checkpoint proteins in immune response

A

Ipilimumab - treatment of advanced melanoma- blocks activity of CTLA4

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6
Q

what activity does Ipilimumab block

A

CTLA4- means cannot complex with B7 on APC- enhancing T cell activation

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7
Q

Immune Checkpoint Protein Inhibition Therapy

- Nivolumab

A

approved for patients with advanced melanoma or advanced lung cancer

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8
Q

Immune Checkpoint Protein Inhibition Therapy

  • pembrolizumab
A

approved for patients with advanced melanoma

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9
Q

TGN1412 is called

A

Theralizumab

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10
Q

TGN1412 was used as an

A

immuno-modulaotry frug for rheumatoid arthritiis

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11
Q

how did TGN1412 work

A

binds to CD28 co-stimualtor pair on T cells

  • potent agonist
  • stimulation inflammatory production

-causes severe inflammatory reaction due to CYTOKINE RELEASE SYNDROME

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12
Q

Adoptive Immune cell therapy: Normal TILs

A

Idea behind this approach is that the TILs have already shown the ability to target tumor cells, but there may not be enough of them within the tumour to eradicate it or overcome the immune suppressive signals that are being released there

Introducing massive amounts of activated TILs can help to overcome these barriers and shrink or destroy tumors

In some experimental cases these treatment responses
have lasted for years

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13
Q

process of using normal TILs to treat tumour cells

A
  • TILs are collected from samples of the tumour
  • TILS that show the greatest recognition of the patients tumour in lab are selected
  • cells are then activated with cytokines and unfused into the patients blood stream
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14
Q

Transgenic TILs

A

T cells are engineered to have a specific transgenic TCR which we know has high affinity to a certain tumour antigen

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15
Q

CAR-T Cells

A

Chimeric Antigen Receptor Modified T cells

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16
Q

how does CAR-T cells therapy work

A
  • a patients isolated T cell are collected for the blood and eugenically modified to express a protein known as CAR
  • CARs are modified forms of T cell receptors- which are expressed on surface of T cell
  • these receptors allow modified T cells to attach to specific proteins on the surface of cancer cells
  • once bound to the cancer cells, the modified T cell come activated and attack the cancer cells
  • modiife cells are grown in lab to produce large pop of cells and then res-infused into patients
17
Q

CARs are

A

are modified forms of T cell receptors- which are expressed on surface of T cell
- these receptors allow modified T cells to attach to specific proteins on the surface of cancer cells

18
Q

tumour antigen specific gene therapy by a gene-modified T lymphocyte: TCR

A

1) sensitive signal amplification derived by evolution
2) low avidity
3) targets intracellular proteasome
4) require MHC class I expression and HLA matching on tumour cell
5) possible mispairing with endogenous TCR

19
Q

tumour antigen specific gene therapy by a gene-modified T lymphocyte: CAR

A

1) signal amplification derived by synthetic biology
2) avidity controllable
3) targets only surface structures
4) HLA independent antigen recognition , universal application
5) no mis-pairing with endogenous TCR