TBL 3 Flashcards

1
Q

What is immunotherapy for cancer?

A

The use of patients own immune system to attack the cancerous tissue.

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2
Q

Immunotherapy uses biological therapeutic agents which can either be ______________ or ________.

A

Antibiotics or Cells

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3
Q

What are the 4 different types of Immunotherapy

A
  • Checkpoint inhibition using monoclonal antibodies
  • Cancer vaccines
  • Administration of antibodies or recombinant proteins to stimulate the immune system
  • Transfer of chimeric antigen receptor (CAR) T cells
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4
Q

What are the 8 Hallmarks of Cancer

A
  1. Sustaining Proliferative Signalling
  2. Evading Growth Suppressors
  3. Resisting Cell Death
  4. Enabling Replicative Immortality
  5. Inducing Angiogenesis
  6. Activating Invasion and Metastasis
  7. Reprogramming Energy Metabolism
  8. Evading Immune Destruction
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5
Q

What are the 5 ways tumours could stop the immune system from destroying them?

A
  1. Tumour cells can lose the expression of MHC class I molecules and therefore cannot present new antigens (e.g. antigens encoded by mutated genes) to T cells.
  2. The tumour develops a way of inhibiting immune responses
  3. Rapid growth may be too much for the immune system to control the tumour
  4. Perhaps the antigenic peptides do not prime the cytotoxic T cells in the correct way
  5. The co-stimulatory molecules required for full T cell activation are not present
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6
Q

What is a neoantigen?

A

A new protein that forms on cancer cells when certain mutations occur in tumour DNA.

Neoantigens may play an important role in helping the body make an immune response against cancer cells.

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7
Q

Which two cytokines are known to be made by tumours to suppress immune cell activity?

A

TGFβ and IL-10

The secretion of these cytokines limit T cell responses which affects the immune response.

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8
Q

Cytotoxic ________ ____ cells are critical for destruction of tumours cells.

A

CD8+ T cells

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9
Q

Where can Tumour-specific CTLs be found?

A

In experimental animals with tumours and in humans with tumours.

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10
Q

Tumour ___________ lymphocytes have the ability to kill tumour cells.

A

Tumour infiltrating lymphocytes (TILs)

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11
Q

Why are CD4+ T helper cells important in the anti-tumour response?

A

They can enhance CD8 T cell responses and macrophage responses by producing key cytokines such as interferon-y and tumour necrosis factor (TNF).

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12
Q

Do Natural Killer Cells (NK cells) recognise cells that do not express MHC Class I or II molecules?

A

MHC Class I

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13
Q

Tumours that have lost expression of MHC Class I are not susceptible to attach by NK cells.
True or False

A

False

  • They are susceptible to attach by NK cells as NK cells recognise cells that do not express MHC Class I molecules.
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14
Q

What are macrophages that are present in the tumour-infiltrating leukocyte population called?

A

Tumour-associated macrophages (TAMs)

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15
Q

What do Tumour-associated macrophages (TAMs) do?

A

They innate immune cells and are capable of killing tumour cells using similar mechanisms to how they kill infectious organisms.

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16
Q

What is required for the activation of a T lymphocyte through the T cell antigen receptor (TCR)?

A

Presentation of a peptide antigen by an MHC molecule.

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17
Q

Which MHC Class is recognised by CD8+ T cells?

A

MHC Class I

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18
Q

Which MHC Class is recognised by CD4+ T cells?

A

MHC Class II

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19
Q

T cells require a second signal through co-stimulatory molecules. Where are stimulatory molecules expressed.

A

On the cell surface of the T cells

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20
Q

Which two molecules does the co-stimulatory molecule CD28 engage with?

A

CD80 or CD86 molecules which are expressed by antigen-presenting cells.

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21
Q

What does signalling through the T cell molecule CD28 do?

A

It enhances the T cell activation process allowing the production of the T cell growth factors IL-2 and beginning the process of clonal proliferation.

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22
Q

Which molecule limits the process of T cell activation?

A

CTLA-4

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23
Q

Which two molecules does the molecule CTLA-4 engage with?

A

CD80 and CD86

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24
Q

What is the cellular outcome of engaging CTLA-4 on the T cell?

A

It is inhibitory. It limits T cell activation

25
Q

What do tumours achieve by expressing proteins that can engage with inhibitory molecules such as CTLA-4?

A

Tumours can evade immune responses and limit T cell responses.

26
Q

What does PD-1 stand for?

A

Programmed cell death protein-1

27
Q

Which two ligands does PD-1 recognise?

A

PD-L1 and PD-L2

28
Q

Engagement of PD-1 on the T cell causes _____________ ____ ______________.

A

Inhibition of activation

29
Q

Which two molecules are responsible for a checkpoint in T cell activation?

A

CTLA-4 and PD-1

30
Q

CTLA-4 is also highly expressed on a population of circulating T cells known as _____________ ___ ______.

A

Regulatory T cells / T-regs

31
Q

What do Regulatory T cells do?

A

They play an important role in suppression of immune responses to prevent autoimmunity.

32
Q

Monoclonal antibodies are used to stop CTLA-4 and PD-1/PD-L1 from engaging with their ligands.

What does this achieve?

A

This effectively stops the T cell inhibition and allows anti-tumour immune responses to proceed.

33
Q

What are the adverse effects of checkpoint inhibitors?

A

Autoimmune and inflammatory reactions. Most frequently these affect the colon, lung, liver and endocrine organs.

34
Q

What are the two major safety concerns for Ipilimumab?

A
  • reports of cytomegalovirus (CMV) gastrointestinal infection or reactivation
  • risk of severe cutaneous adverse reactions (SCARs)
35
Q

Why is vaccination typically undertaken for immunotherapy?

A

To boost immune responses to particular antigens such as infectious organisms.

36
Q

In cancer, what is the aim of vaccination?

A

To boost the cytotoxic CD8+ T cell response that recognise the tumour cells.

37
Q

What three things can the vaccine consist of?

A
  • Killed tumour cells from the patient
  • Recombinant tumour antigens
  • Dendritic cell vaccines
38
Q

How are dendritic cell vaccines made and how does it work?

A

Dendritic cells are taken from the patients and incubated with tumour antigens in a lab (ex vivo). The dendritic cells are then injected back into the patient allowing the dendritic checks to present the tumour antigen to T cells.

39
Q

Many of the clinical trials that have been performed to test cancer vaccines have yielded inconsistent results. What may be the reason for this.

A

This may be due to the tumours ability to evade immune responses.

40
Q

In the future, cancer vaccines may be more successful if given as a combination therapy with what kind of drugs?

A

Checkpoint inhibitors

41
Q

What does “Oncogenesis” mean?

A

Oncogenesis is the process through which healthy cells become transformed into cancer cells.

42
Q

_______________ vaccination can also be performed with viral antigens that are known to be oncogenic.

A

Preventative vaccination.

43
Q

Who is eligible for the vaccine against HPV?

A
  • Children who are 12 to 13 years of age
  • gay, bisexual and other men who have sex with men (MSM) up to 45 years of age.
44
Q

Anti-CD20 antibodies can be used to deplete all cells expressing which cell surface marker?

A

CD20 - A cell surface marker of B cells

45
Q

Which growth factor receptors do antibodies to breast cancer antigens target?

A

Her2 and EGFR

46
Q

How does administering cytokines boost host immune responses to tumours?

A

They are known to stimulate T cells and NK cells or to enhance the activation of dendritic cells.

47
Q

What is used clinically to treat melanoma and renal cell carcinoma?

A

Interleukin-2 (IL-2)

48
Q

How is Interleukin-2 usually given and what does it do?

A

It is given at a high dose and can stimulate production of inflammatory cytokines such as TNF-a and IFN-y which can cause serious side effects.

49
Q

Name three cancers Interferon-a (IFN-a) can be used to treat.

A
  • Melanoma
  • Lymphomas
  • Leukaemias
50
Q

How does Interferon-a (IFN-a) work?

A

This cytokine will increase the action of NK cells and help up regulate MHC class I expression on tumour cells thus promoting the cytotoxic action of CD8+T cells.

51
Q

What is adoptive therapy?

A

Immune cells are derived from the patients blood and expanded in vitro before being reinfused into the patient.

52
Q

What are Chimeric antigen receptors (CARs)?

A

They are genetically engineered receptors which have specific antigen-binding sites allowing the treatment to be directed to a specific tumour-bearing antigen.

53
Q

CARs are chimera’s of which sources?

A

Immunoglobulin variable gene and the cytoplasmic tails containing the relevant signalling domains of the TCR and co-stimulatory molecules.

This includes the ITAM of a TCR and the intracellular signalling domain of CD28.

54
Q

How do CAR T-cells work?

A
  1. Peripheral blood is taken from the patient and T cells are isolated.
  2. The T cells are then put to culture and be stimulated to expand using antibodies to the CD3 complex and antibodies to the CD28 co-stimulatory molecule.
  3. The expanded T cells are then transfected with viral vectors encoding the genetically engineered CAR.
  4. The T cells are then injected back into the patient where it undergoes further proliferation in response to tumour antigen recognition events by the newly expressed CAR.
55
Q

Which type of cancer have been successfully treated using CAR T cell therapy?

A

B cell malignancies such as lymphoma

56
Q

CAR T cells recognise which B cell surface marker?

A

CD19

57
Q

What is lymphoma?

A

Lymphoma is a type of blood cancer

58
Q

CAR T-cell therapy can cause an intense systemic inflammatory response or cytokine release syndrome. Why?

A

This is due to the high number of activated T cells in the patient.