Protein applications in biomedicine

Question 1

What are some roles for proteins in biomedicine?

Answer 1

Therapeutics
Biomarkers
Lab tests

Question 2

What are therapeutic proteins?

Answer 2

Therapeutic proteins can augment/replace/introduce enzyme activities
Proteins form very specific interactions with other biomolecules (especially antibodies)
Can be engineered to modify properties and provide novel functions

Question 3

What are type 1 therapeutic proteins?

Answer 3

proteins with enzymatic or regulatory activity

Question 4

Give some examples of Type 1 therapeutic proteins

Answer 4

Insulin
Pancrelipase
alpha1 - antitrypsin

Question 5

What would therapeutic proteins with enzymatic or regulatory activity be used for?

Answer 5

Replace a deficient/abnormal protein
Augment an existing pathway
Provide a novel activity/function

Question 6

What are type 2 therapeutic proteins?

Answer 6

Proteins with special targeting activity

Question 7

What are type 2 proteins used for?

Answer 7

Targeting disease cells
Inhibit specific pathogenic proteins/pathways
used to deliver other compounds
Blocking protein-protein interactions

Question 8

Give some examples of type 2 therapeutic proteins

Answer 8

Brentuximab vedotin - cargo delivery drug to deliver monomethyl auristatin E
Herceptin - targets HER2 oncoprotein and blocks down regulation stream of HER2 signalling
Immune checkpoint inhibitors - Nivolumab which is an Ab that blocks PD1-PDL1 interactions for cancer treatment.

Question 9

What are the challenges with using therapeutic proteins?

Answer 9

Efficacy/Safety

Immunogenicity – immune response may limit efficacy (or worse)

Cannot permeate cell membranes (currently)

Safe production and cost (can be overcome by using recombinant proteins)

Delivery – injection/infusion required (oral administration = digestion rather than absorption)

Question 10

What is a biomarker?

Answer 10

a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention

Question 11

What are the functions of biomarkers?

Answer 11

Diagnostic biomarkers - detect presence of disease

Prognostic biomarkers - indicate aggression of disease and may determine treatment

Predictive biomarkers - match drugs to patients for personalised or precision medicine.

Question 12

How can proteins be used in laboratory tests?

Answer 12

Most use ELISA or antibody based methods

These tests must be standardised

Question 13

What are some non-specific biomarkers?

Answer 13

CRP (C-reactive protein)
Made in liver
Binds to phosphocholine
Activates complement cascade

Question 14

Give some diagnostic biomarker examples

Answer 14

Tissue/organ specific (eg. Albumin) - Major component of serum, made in liver
Decreased levels in chronic liver disease

Serum markers - Cardiac tissue damage

Immunoassay for tissue specific markers - Point of care testing

Question 15

Give some examples of prognostic protein biomarkers

Answer 15

Prostate specific antigen (PSA) - Cancer biomarker
high levels indicate prostate cancer
medium levels could be benign hyperplasia

Alpha fetoprotein (AFP) - Oncofetal antigens:
Not normally expressed in adults
Chronic liver disease causes increase in AFP

Question 16

How can biomarkers test for sensitivity and specificity?

Answer 16

Sensitivity - % of disease cases correctly identified

Specificity - % of non-diseased cases correctly identified

Question 17

give some uses of Immunohistochemistry protein biomarkers

Answer 17

In cancer:

Aid to diagnosis
Cancer subtyping
Tissue of origin
Prognosis (how aggressive a tumour is)
Predicting response to treatment
Enable stratified/personalised/precision medicine

Question 18

Give examples of predictive protein biomarkers

Answer 18

HER2 - Predictive biomarker for Herceptin
Herceptin only works when HER2 receptors are present

TMPT - Predicts toxicity used in treatment of autoimmune diseases