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Cancer Biology (BIO-6009A) > Lecture 12: Immunotherapy > Flashcards

Lecture 12: Immunotherapy Flashcards

1
Q

What is meant by immunomodulation?

A

IMMUNE POTENTIATORS (extrinsic): tumours may regress when a cancer patient develops an infection (known since 1800s)

William Coley (1893): deliberately infected cancer patients with bacteria, sometimes able to cure the patient of all signs of cancer

BCG Vaccine (Pacis): utilized using this concept for localized bladder cancer post surgery

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2
Q

What are the main categories of cancer immuno-therapy?

A
  1. Cancer vaccines
  2. Cytokine therapies
  3. Adoptive cell transfer
  4. Immune checkpoint inhibitors
  5. Oncolytic virus therapies
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3
Q

What are cytokine therapies?

A
  1. IMMUNOMODULATION: biological response modifiers (intrinsic)
    e.g., IL-1 and IL-2, IFN alpha, beta, gamma, TNF, B-cell, &
    haematopoietic growth factorsCan be: injected into patient or used ex vivo to transform patients
    lymphocytes into ‘lymphokine-activated killer cells’ and ‘tumour-
    infiltrating lymphocytes’, injected back into patient
  2. NON-SPECIFIC IMMUNO-STIMULATION
    a. IL-2: increased activation, proliferation, survival & effector functions
    of T-cells
    b. IFNs: increased T cells, NK toxicity, Fc receptors, ADCC, B cell
    proliferation & antibody production
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4
Q

How can ipilimumab and nivolumab help stop cancef?

A

Can stop cancers hiding, allowing the immune system to attack

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5
Q

How does adoptive T-cell therapies work?

A
  1. T-cells from proliferation blood
  2. Viral or non-viral insertion of genes into T-cells
    3a. T-cell receptor (TCR): Antigen processed and presented by MHC
    3b. Chimeric antigen receptor (CAR): Antigen expressed on the cell
    surface
  3. Expand TCR gene-engineered T-cells
  4. Cell infusion with IL-2
  5. Preconditioning with chemotherapy
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6
Q

What are cancer vaccines?

A

Majority used for treatment not prevention

May enhance immune response against cancer

Different to traditional vaccines

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7
Q

What are different types of cancer vaccines?

A

Tumour cell vaccines (autologous vs allogenic)
Dendritic cell vaccines
Antigen vaccines
Anti-idiotypic vaccines
DNA vaccines

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8
Q

What are tumour cell vaccines?

A
  1. Utilize whole tumour cells rendered sage by irradiation
  2. Specific IR initiated when injected into body
  3. Body attacks similar cells that remain in the body
  4. AUTOLOGOUS-REMOVED TUMOUR CELLS: from patients own body
  5. ALLOGENIC-REMOVED TUMOUR CELLS: from other people
  6. Many different epitopes recognized
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9
Q

How can tumour cell vaccines be modified

A

1.Can be genetically modified to secrete specific cytokines

A. secreted locally, attract antigen presenting cells, processes specific
tumour antigens and present them on their surface MHC molecules
B. antigens, when bound to MHC molecules, stimulated T-cells to
proliferate or become lyric by engaging T-cell receptor

  1. Tumour cells can also be generate to express MHC class 1 or 2 molecules and/or B7. This means CD4+ and or CD8+ T-cells can be activated directly by tumour cell itself
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10
Q

What are dendritic cell vaccines?

A
  1. Dendritic cells (APCs) can be generated outside the body
  2. Dendritic cells are made capable of recognizing antigen by gene
    therapy and exposure to antigen
  3. Dendritic cells injected into individual stimulating an immune response
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11
Q

What are antigen vaccines?

A
  1. includes peptide vaccines: only one specific epitope injected
  2. vast amounts of antigen can be created in labs
  3. some antigens are specific for a certain type of cancer; others may
    induce an immune response in several cancers
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12
Q

What are anti-idiotypic vaccines?

A
  1. Idea that Abs can also act as Ags triggering an IR
  2. Vaccine in which the Antibodies (resembling cancer antigens) are
    injected into cancer patient eliciting response
  3. E.g., Racotumomab. mouse monoclonal antibody that mimics NGc
    gangliosides, thus immune response against tumour antigen NGcGM3
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13
Q

What are DNA vaccines?

A
  1. introduction of tumour genes instead of tumour antigen itself
  2. Cells in the body take up the injected DNA
  3. Specific antigens would then be made on a continual basis
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14
Q

What are oncolytic virus therapies?

A

Typically: genetically modified viruses to infect tumour cells, to lyse the cancer cells and stimulate a proinflammatory environment o augment systemic antitumor immunity

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15
Q

What are the different modes of effect by oncolytic viruses

A
  1. Amplification of oncolytic
  2. nutrient / oxygen deprivation
  3. Tumour vaccination
  4. Gene therapy
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16
Q

What are some other antibody-based immunotherapies?

A

“Blockade of ligand-receptor binding, increased ADCC, complement immunoconjugates - drug or radioisotope

17
Q

What is herceptin?

A

Can be used to kill breast cancer cells

Cancer Biology (BIO-6009A) (24 decks)

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