Biologics: monoclonal antibodies MCQs With Answer

Introduction: This collection of multiple-choice questions focuses on biologics — specifically monoclonal antibodies (mAbs) — tailored for M.Pharm students studying Biological Evaluation of Drug Therapy. The quiz covers fundamental and advanced topics such as antibody structure and isotypes, mechanisms of action (ADCC, CDC, checkpoint inhibition), production technologies (hybridoma, phage display), Fc and glycoengineering, pharmacokinetics (FcRn recycling, target-mediated disposition), immunogenicity assessment (ADA detection, neutralization assays), and regulatory considerations for biosimilars and ADCs. These questions are designed to deepen conceptual understanding, test application-level knowledge, and prepare students for examinations and practical evaluation of therapeutic antibodies.

Q1. Which mechanism primarily mediates antibody-dependent cellular cytotoxicity (ADCC) by therapeutic IgG?

• Fab region crosslinking on tumor cells leading to apoptosis
• Fc region binding to FcγRIIIa on natural killer (NK) cells
• Complement C1q binding to the Fc region initiating the complement cascade
• Neonatal Fc receptor (FcRn) recycling prolonging serum half-life

Correct Answer: Fc region binding to FcγRIIIa on natural killer (NK) cells

Q2. The hybridoma technique for producing monoclonal antibodies involves which key step?

• Immunizing phage libraries and selecting binders in vitro
• Fusing antibody-producing B lymphocytes with immortal myeloma cells
• Cloning full-length human IgG sequences directly from peripheral blood
• Expressing single-chain variable fragments (scFv) in bacterial systems

Correct Answer: Fusing antibody-producing B lymphocytes with immortal myeloma cells

Q3. In monoclonal antibody nomenclature, which suffix indicates a chimeric antibody?

• -umab (fully human)
• -zumab (humanized)
• -ximab (chimeric)
• -omab (murine)

Correct Answer: -ximab (chimeric)

Q4. What is the primary role of the neonatal Fc receptor (FcRn) in monoclonal antibody pharmacokinetics?

• Promoting antibody-dependent cellular cytotoxicity
• Binding IgG at acidic pH and recycling it to extend serum half-life
• Facilitating renal filtration of small antibody fragments
• Mediating complement activation via C1q recruitment

Correct Answer: Binding IgG at acidic pH and recycling it to extend serum half-life

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

• Increases complement-dependent cytotoxicity (CDC) by enhancing C1q binding
• Enhances ADCC by increasing affinity for FcγRIIIa
• Improves FcRn binding and prolongs half-life
• Reduces aggregation propensity by increasing solubility

Correct Answer: Enhances ADCC by increasing affinity for FcγRIIIa

Q6. Compared with hybridoma methods, what is a principal advantage of phage display for antibody discovery?

• Generates full-length glycosylated IgG directly in bacterial hosts
• Allows selection of human antibody fragments in vitro without animal immunization
• Eliminates the need for subsequent affinity maturation
• Always produces antibodies with optimal pharmacokinetics

Correct Answer: Allows selection of human antibody fragments in vitro without animal immunization

Q7. Which assay is most appropriate for detecting functional neutralizing anti-drug antibodies (nADAs) against a therapeutic monoclonal antibody?

• Indirect ELISA measuring total binding antibodies
• Bridging ELISA detecting anti-drug IgG
• Cell-based neutralization assay that measures inhibition of drug activity
• Western blot detecting antibody binding to denatured drug

Correct Answer: Cell-based neutralization assay that measures inhibition of drug activity

Q8. An antibody–drug conjugate (ADC) typically consists of which three components?

• Antibody, cytokine adjuvant, and PEGylation
• Antibody, cytotoxic payload, and a cleavable or non-cleavable linker
• Fab fragment, Fc fragment, and albumin binding domain
• Monoclonal antibody, checkpoint inhibitor, and adjuvant

Correct Answer: Antibody, cytotoxic payload, and a cleavable or non-cleavable linker

Q9. Which human IgG subclass has the highest intrinsic ability to activate complement (C1q binding)?

• IgG1
• IgG2
• IgG3
• IgG4

Correct Answer: IgG3

Q10. Which Fc modification is commonly used to reduce Fcγ receptor binding and thereby decrease effector function?

• Afucosylation of the Fc N-glycan
• L234A/L235A (LALA) point mutations in the Fc region
• Introduction of additional N-glycosylation sites in the Fab
• PEGylation of the Fc to increase hydrodynamic size

Correct Answer: L234A/L235A (LALA) point mutations in the Fc region

Q11. For a monoclonal antibody biosimilar, regulatory comparability must generally include which elements?

• Only clinical efficacy trials are required
• Analytical similarity, functional assays, PK/PD, and immunogenicity assessment
• Identical manufacturing process to the reference product
• Only in vitro binding assays and literature bridging

Correct Answer: Analytical similarity, functional assays, PK/PD, and immunogenicity assessment

Q12. The principal mechanism of action of anti–PD-1 monoclonal antibodies in cancer therapy is:

• Direct induction of tumor cell apoptosis via complement activation
• Blocking the PD-1/PD-L1 inhibitory pathway to restore T-cell effector function
• Delivering cytotoxic payloads selectively to tumor vasculature
• Activating NK cells through FcγR crosslinking

Correct Answer: Blocking the PD-1/PD-L1 inhibitory pathway to restore T-cell effector function

Q13. Which factor most strongly influences the bioavailability of subcutaneously administered monoclonal antibodies?

• Glomerular filtration rate
• Lymphatic uptake and proteolytic degradation at the injection site
• Hepatic first-pass metabolism
• Renal tubular secretion

Correct Answer: Lymphatic uptake and proteolytic degradation at the injection site

Q14. Glycosylation at Asn297 in the IgG Fc region primarily modulates which functions?

• Antigen binding affinity of the Fab
• Fcγ receptor binding and complement activation affecting ADCC and CDC
• Molecular weight but not effector functions
• Renal clearance through mannose receptors only

Correct Answer: Fcγ receptor binding and complement activation affecting ADCC and CDC

Q15. Clearance of monoclonal antibodies in humans commonly involves which two mechanisms?

• Glomerular filtration and active renal secretion
• Target-mediated drug disposition (TMDD) and nonspecific proteolytic catabolism
• Hepatic cytochrome P450 metabolism and biliary excretion
• Acetylation and glucuronidation in the liver

Correct Answer: Target-mediated drug disposition (TMDD) and nonspecific proteolytic catabolism

Q16. Which strategy is commonly employed to reduce immunogenicity of a therapeutic monoclonal antibody?

• Converting all glycosylation sites to high-mannose glycans
• Humanization or deimmunization to remove non-human T-cell epitopes
• Increasing murine sequence content to improve stability
• Administering antibody only via intramuscular route

Correct Answer: Humanization or deimmunization to remove non-human T-cell epitopes

Q17. Which analytical technique is most informative about the higher-order (tertiary/quaternary) structure and thermal stability of a monoclonal antibody?

• SDS-PAGE under reducing conditions
• Differential scanning calorimetry (DSC)
• Standard ELISA for antigen binding
• Size-exclusion HPLC measuring monomer content only

Correct Answer: Differential scanning calorimetry (DSC)

Q18. How does a single-chain variable fragment (scFv) differ from a Fab fragment?

• scFv contains the constant Fc region while Fab lacks it
• scFv is a single polypeptide linking VH and VL domains and lacks the Fc region
• Fab is monovalent but scFv is always bivalent
• Fab is produced only by phage display while scFv is produced by hybridomas

Correct Answer: scFv is a single polypeptide linking VH and VL domains and lacks the Fc region

Q19. Which statement best distinguishes neutralizing anti-drug antibodies (nADAs) from non-neutralizing ADAs?

• nADAs only increase clearance while non-neutralizing ADAs block biological activity
• nADAs block the drug’s biological activity and may affect efficacy; non-neutralizing ADAs mainly alter clearance or distribution
• Non-neutralizing ADAs always form immune complexes that activate complement
• nADAs are detected only by bridging ELISA whereas non-neutralizing ADAs are detected only by cell assays

Correct Answer: nADAs block the drug’s biological activity and may affect efficacy; non-neutralizing ADAs mainly alter clearance or distribution

Q20. For first‑in‑human dose selection of a novel monoclonal antibody with potential biological activity, regulators commonly recommend basing dose on:

• No observed adverse effect level (NOAEL) from rodent studies alone
• Minimum anticipated biological effect level (MABEL) informed by in vitro potency, receptor occupancy and PK/PD
• Maximum tolerated dose established in healthy volunteers
• A fixed mg/kg dose extrapolated from marketed products without additional data

Correct Answer: Minimum anticipated biological effect level (MABEL) informed by in vitro potency, receptor occupancy and PK/PD

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