L13 Uses of mAbs - therapeutics Flashcards
Understand how the characteristics of monoclonal and polyclonal antibodies influence how they are used. Discuss the applications of rodent monoclonal antibodies. Review 'on site' assays. Know how monoclonals are used in immunoaffinity purification, as research tools and as anti-toxins. Know how monoclonal antibodies are currently used therapeutically, and appreciate their future potential.
How can mAbs be used as anti-toxins?
By binding and neutralising toxins in body, e.g. tetanus.
Tetanus immune globulin (TIG) provides temp. passive immunity to tetanus. Not immunogenic, no immunity to tetanus given though.
Anti-ricin antibodies also developed.
What are anti-idiotype antibodies?
Antibodies that target the CDR of another antibody. Very similar structure to the target antibodies antigen.
How are anti-idiotype vaccines used in cancer therapy?
Targetting a tumour associated antigen, primary and then anti-idiotype antibody given. Enhances secondary immune response. Good in targeting cancer.
How can anti-idiotypic antibodies also target antibodies w/o targeting CDR?
Targeting non-site specific section of the variable region of the target antibody.
What are the three therapeutic applications of mAbs?
Cancer
Immunosuppression
Infectious disease
What two ways can mAbs be used in therapies?
Either naked, activating complement or recruiting NK/monocytes to kill target cell.
Conjugated to toxins, radiolabel, etc.
Mabs in cancer therapy - table
How can radiolabelled mAbs be used in cancer therapy?
Selectively irradiates cancer cells, thus kills them.
Used more to remove residual tissue after surgery/chemotherapy.
What is antibodiy directed enzyme prodrug therapy (ADEPT)?
Enzyme conjugated to antibody, with Ab directed against tumour associated antigen.
Given alongside a systemic pro-drug.
At site of tumour, pro-drug converted to toxic molecule by conj. enzyme.
Only in phase I trials.
Which cytokine has been conj. to mAbs in phase 1 trial?
IL-2 conjugate
Mabs in treatment of infectious disease
Mabs in immunosuppression
What is TRAPS, and what issue does it cause with mAb therapy?
Rare disease, associated with inability to shed TNF from receptor.
If antibodies are used in these patients, TNF signal remains constitutively on.
Pathological inflammation seen.
How does the use of antibody fragments minimise issues associated with mAb therapy?
Without Fc region, antibodies can just neutrialise the target without inducing immune response. Can be desired in some settings, but not cancer.
