Lecture 12: Immunotherapy

Question 1

What is meant by immunomodulation?

Answer 1

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

Question 2

What are the main categories of cancer immuno-therapy?

Answer 2

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

Question 3

What are cytokine therapies?

Answer 3

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

Question 4

How can ipilimumab and nivolumab help stop cancef?

Answer 4

Can stop cancers hiding, allowing the immune system to attack

Question 5

How does adoptive T-cell therapies work?

Answer 5

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

Question 6

What are cancer vaccines?

Answer 6

Majority used for treatment not prevention

May enhance immune response against cancer

Different to traditional vaccines

Question 7

What are different types of cancer vaccines?

Answer 7

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

Question 8

What are tumour cell vaccines?

Answer 8

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

Question 9

How can tumour cell vaccines be modified

Answer 9

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

2. 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

Question 10

What are dendritic cell vaccines?

Answer 10

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

Question 11

What are antigen vaccines?

Answer 11

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

Question 12

What are anti-idiotypic vaccines?

Answer 12

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

Question 13

What are DNA vaccines?

Answer 13

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

Question 14

What are oncolytic virus therapies?

Answer 14

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

Question 15

What are the different modes of effect by oncolytic viruses

Answer 15

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

Question 16

What are some other antibody-based immunotherapies?

Answer 16

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

Question 17

What is herceptin?

Answer 17

Can be used to kill breast cancer cells