Monoclonal antibodies in targeting MCQs With Answer

Monoclonal antibodies in targeting MCQs With Answer

This quiz collection is designed for M.Pharm students studying Molecular Pharmaceutics/NTDS to deepen understanding of monoclonal antibodies (mAbs) as targeted therapeutics. The questions cover antibody structure and isotypes, mechanisms of action (ADCC, CDC, neutralization), pharmacokinetics (FcRn salvage, half-life modulation), engineering strategies (humanization, glycoengineering, bispecifics), antibody–drug conjugates (linkers, payloads, DAR), manufacturing considerations, and immunogenicity. Each question challenges conceptual and applied knowledge, linking molecular design decisions to clinical performance and formulation considerations. Use these MCQs for exam practice, classroom discussion, or self-assessment to build competence in designing and evaluating antibody-based targeted therapies.

Q1. Which Fc property primarily determines the long serum half-life of IgG monoclonal antibodies?

• Affinity for Fc gamma receptors on NK cells
• Binding to neonatal Fc receptor (FcRn) and recycling
• Ability to fix complement by C1q binding
• Degree of antigen affinity of the Fab region

Correct Answer: Binding to neonatal Fc receptor (FcRn) and recycling

Q2. Which antibody isotype is most commonly engineered for therapeutic monoclonal antibodies when effector functions like ADCC and CDC are desired?

• IgA
• IgM
• IgG1
• IgG4

Correct Answer: IgG1

Q3. Humanization of a murine monoclonal antibody primarily reduces which of the following risks?

• Loss of antigen specificity
• Formation of anti-drug antibodies (immunogenicity)
• Increased complement activation
• Enhanced FcRn binding and half-life

Correct Answer: Formation of anti-drug antibodies (immunogenicity)

Q4. Which technique enables production of fully human monoclonal antibodies without using human donors?

• Hybridoma using mouse myeloma cells only
• Phage display libraries and selection
• PEGylation of murine antibodies
• Complement fixation assay

Correct Answer: Phage display libraries and selection

Q5. Afucosylation of the Fc N-glycan on IgG therapeutics most directly affects which functional property?

• Antigen-binding affinity of the Fab
• Complement-dependent cytotoxicity (CDC)
• Antibody-dependent cellular cytotoxicity (ADCC)
• TRAIL receptor activation

Correct Answer: Antibody-dependent cellular cytotoxicity (ADCC)

Q6. Which statement best describes a bispecific T-cell engager (BiTE) antibody format?

• A full-length IgG that blocks two soluble cytokines simultaneously
• A single-chain construct that links tumour cell antigen-binding to CD3 on T cells
• An IgM pentamer engineered to enhance complement activation
• An ADC with two different cytotoxic payloads

Correct Answer: A single-chain construct that links tumour cell antigen-binding to CD3 on T cells

Q7. In antibody–drug conjugates (ADCs), what is the primary role of a cleavable linker compared to a non-cleavable linker?

• Improve systemic stability to prevent release in target cells
• Allow intracellular release of the cytotoxic payload after internalization
• Reduce payload potency to minimize off-target toxicity
• Increase antibody half-life by preventing FcRn binding

Correct Answer: Allow intracellular release of the cytotoxic payload after internalization

Q8. Which parameter describes the average number of drug molecules attached per antibody in an ADC?

• Antibody affinity constant (Ka)
• Drug-to-antibody ratio (DAR)
• Fc gamma receptor occupancy
• Isoelectric point (pI)

Correct Answer: Drug-to-antibody ratio (DAR)

Q9. Which manufacturing host cell line is most widely used for producing therapeutic monoclonal antibodies at commercial scale?

• Escherichia coli
• Saccharomyces cerevisiae
• Chinese Hamster Ovary (CHO) cells
• Human embryonic kidney (HEK293) only

Correct Answer: Chinese Hamster Ovary (CHO) cells

Q10. Glycoengineering to produce afucosylated antibodies is primarily performed to enhance which clinical effect?

• Reduce blood clearance via FcRn
• Increase ADCC efficacy against target cells
• Prevent antigen binding off-target
• Improve complement activation by C1q

Correct Answer: Increase ADCC efficacy against target cells

Q11. Which factor most reduces tissue penetration of full-length IgG antibodies in solid tumors?

• Small molecular size (~25 kDa)
• High affinity causing perivascular binding (binding-site barrier)
• Lack of FcRn-mediated recycling
• Absence of glycosylation

Correct Answer: High affinity causing perivascular binding (binding-site barrier)

Q12. Which mechanism best explains complement-dependent cytotoxicity (CDC) mediated by certain therapeutic IgGs?

• Recruitment of NK cells via FcγRIIIa binding
• Direct induction of apoptosis through Fas receptor binding
• Activation of C1q after antibody clustering on the cell surface leading to MAC formation
• Blocking cytokine receptors to inhibit survival signals

Correct Answer: Activation of C1q after antibody clustering on the cell surface leading to MAC formation

Q13. Which modification is commonly used to extend antibody half-life beyond natural IgG half-life?

• Removing all Fc glycosylation sites
• FcRn-binding affinity enhancement via Fc engineering
• Conversion to IgM isotype
• Conjugation with a membrane anchor peptide

Correct Answer: FcRn-binding affinity enhancement via Fc engineering

Q14. Antibody human anti-chimeric antibody (HACA) or human anti-humanized antibody (HAHA) responses are examples of which problem in therapeutic mAbs?

• Target-mediated drug disposition
• On-target toxicity
• Immunogenicity leading to neutralization or clearance
• Reversible aggregation improving potency

Correct Answer: Immunogenicity leading to neutralization or clearance

Q15. Which of the following best characterizes a single-chain variable fragment (scFv)?

• Full-length IgG with intact Fc region
• Two separate heavy chains without light chains
• A small engineered fragment linking VH and VL domains by a peptide linker
• A pentameric secreted antibody found in mucosal surfaces

Correct Answer: A small engineered fragment linking VH and VL domains by a peptide linker

Q16. For an antibody targeting a cell-surface receptor that must deliver a cytotoxic payload intracellularly, which property is most desirable?

• High ability to activate complement without internalization
• Efficient receptor-mediated internalization upon antigen binding
• Exclusive binding to soluble antigen in plasma
• Very slow dissociation to prevent internalization

Correct Answer: Efficient receptor-mediated internalization upon antigen binding

Q17. Which clinical example is a monoclonal antibody that targets VEGF to inhibit angiogenesis?

• Trastuzumab
• Bevacizumab
• Rituximab
• Cetuximab

Correct Answer: Bevacizumab

Q18. When designing site-specific conjugation for ADCs, which advantage is most important compared to random conjugation?

• Increased heterogeneity in DAR distribution
• Better control of pharmacokinetics and consistent potency
• Higher risk of immunogenic hinge modification
• Loss of FcRn binding in all molecules

Correct Answer: Better control of pharmacokinetics and consistent potency

Q19. Checkpoint inhibitor antibodies that block PD-1/PD-L1 interactions primarily restore which immune function against tumours?

• Complement activation by B cells
• T-cell mediated anti-tumour cytotoxicity
• NK cell maturation in bone marrow
• Neutralization of circulating toxins

Correct Answer: T-cell mediated anti-tumour cytotoxicity

Q20. Which analytical attribute is critical to monitor during mAb formulation development to ensure stability and reduced immunogenicity?

• Chromatographic retention time of free drug only
• Aggregate formation, fragmentation, and post-translational modifications
• Electrical conductivity of the buffer exclusively
• Presence of antibiotic residues in the final product

Correct Answer: Aggregate formation, fragmentation, and post-translational modifications

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