Immunotherapies

Question 1

What are immunotherapies based on?

Answer 1

Immunomodulation

either suppression or activation

Question 2

Therapeutic molecules

Answer 2

1. Small molecules: <500 Da, non-protein
2. MAb(monoclonal antibodies)
3. Therapeutic proteins: EC ligands/receptors e.g IL-2
4. Vaccines, IVIG: stim endogenous ab prod or give passive ab dosage
5. Immune cell based therapies e.g dendritic cell therapy

Question 3

Immunotherapies: Main areas of application

Answer 3

1. Anti-tumor
2. Autoimmunity
3. Immunodeficiencies
4. Transplantation
5. Allergies
6. Autoinflamm diseases

Question 4

MAb= Monoclonal Antibodies

Answer 4

Bind to a specific epitop
Whole or fragment ab
Modified by conjugation- toxins, radioactive substances, binding of cytokines
Used for both suppression and stimulation
Can be bispecific: they can connect the target and effector cell

Question 5

MAb effector functions

Answer 5

Neutralization
Receptor blocking
Apoptosis through cross reactions

Question 6

Production of MAb: cell types

Answer 6

Plasma cells

Myeloma cells

Question 7

Production of MAb plasma cells

Answer 7

No in vitro propagation
Retrieved from spleen of an immunized mouse
Ab production

Question 8

Production of MAb myeloma cell

Answer 8

Propagation in vitro
No ab production
No HGPRT
No TK

Question 9

Selection of the MAb

Answer 9

Select the viable clones with hypoxanthine aminopterin

Selection of clones producing the desired abs with immuno tests e.g ELISA, IF

Question 10

Production of MAb

Answer 10

In vivo

In vitro

Question 11

Production of MAb: In vivo

Answer 11

Abdominal fluid
Possibility of contamination
Animal welfare considerations

Question 12

Production of MAb: In vitro

Answer 12

Supernatant
Lower risk of contamination
Similar amounts can be obtained

Question 13

Labelling antibodies

Answer 13

Fab labelled or

Fc labelled

Question 14

Labelling antibodies: Fab labelled

Answer 14

Biclonal!
Effector cell and antigen
Fusion protein and antigen

Question 15

Labelling antibodies: Fc labelled

I think these are used in therapy?

Answer 15

Drugs: tumors, autoimmune
Toxin: cytotoxic 
Cytokine: APC activity up
Radioactive substances: diagnostics and tumors 
Liposome: drug
Enzyme: diagnostics 
Fluorescent dye: diagnostics 
Biotin: diagnostics

Question 16

Application od MAb

Answer 16

Research
Diagnostics
Therapy

Question 17

MAb diagnostics

Answer 17

Targets: bacteria, viruses, antibodies, tumors
Methods: ELISA, immunohistochem, immunofluorescence

Question 18

MAb therapy

Answer 18

Direct cytotoxicity or cell function modulation

Question 19

The dangers of MAb therapies

Answer 19

Short term: acute hyperreactivity- anaphylaxis
Long-term: elimination of the adaptive immune response

Solution: genetic engineering to produce humanized MAb
Use of ab fragments
Absence of Fc region reduces nonspecific binding

Question 20

MAb therapy: Mechanisms of action

Answer 20

Ligand binding 
Receptor blocking
Receptor down reg
Depletion
Signal induction
Apoptosis induction
Labelling with toxins or drugs

Question 21

MAb therapy: areas of application

Answer 21

Inflamm diseases
Autoimmune diseases
Infectious diseases
Tumors

Question 22

MAb in inflamm diseases

Answer 22

Chronic inflamm-
Psoriasis: combined cytokine neutralization anti-p40 ab
Chron’s disease, sclerosis multiplex: anti-integrin alpha4

Question 23

MAb in Autoimmune diseases, transplantation, tumours

Answer 23

Before organ transplatation, chronic lymphoid leukemia, T-cell lymphomas
Elimination of mature lymphocytes
Anti CD52 ab

Question 24

Cancer immunotherapy

Answer 24

Therapeutic vaccination
Active vaccination: injection of tumor antigens
Passive vaccinaiton: injection of ab or cells