Pharmacology researchers develop a novel monoclonal antibody medication to treat the wet form of age-related macular degeneration. The antibody binds vascular endothelial growth factor, decreasing abnormal blood vessel formation in the subretinal space. In a clinical trial, the medication is found to improve visual function. During the next phase of the study, researchers use only the antigen binding fragment (Fab) of the antibody instead of the whole immunoglobulin. Which of the following is most likely to be observed with use of the antibody fragments compared to the intact immunoglobulin?

Question

Pharmacology researchers develop a novel monoclonal antibody medication to treat the wet form of age-related macular degeneration.  The antibody binds vascular endothelial growth factor, decreasing abnormal blood vessel formation in the subretinal space.  In a clinical trial, the medication is found to improve visual function.  During the next phase of the study, researchers use only the antigen binding fragment (Fab) of the antibody instead of the whole immunoglobulin.  Which of the following is most likely to be observed with use of the antibody fragments compared to the intact immunoglobulin?

Quizplus · Accepted Answer

11ec160b_37b2_83ec_9249_0f8710634e4a_MD0001_00 Immunoglobulins (antibodies) are the principal component of the humoral immune system. They are effector proteins that bind to specific epitopes of antigens based on the unique group of 110-130 amino acids present in the hypervariable region of the immunoglobulin light and heavy chain. Because individual immunoglobulins can identify molecular targets with a high degree of specificity, immunoglobulin therapy (immunotherapy) has been developed to target specific ligands, cytokines, receptors, growth factors, and other proteins that contribute to the pathogenesis or progression of inflammatory and neoplastic conditions. Immunotherapy is monoclonal because all the immunoglobulin components in the medication have the same hypervariable region (produced from the same B-cell clone). However, most immunotherapy regimens use a fragment of the immunoglobulin with 1 valence (binding) site rather than the full immunoglobulin with 2 valence sites, because fragments are significantly smaller than the full immunoglobulin, which improves tissue/tumor penetration and medication pharmacokinetics. Common types of immunoglobulin fragments include the following: Antigen binding fragments (Fab) contain a variable domain and the first constant region of a heavy and light chain. Because Fab fragments do not contain an Fc region, they do not activate complement or trigger phagocytosis via the Fc receptor on macrophages (Choices C and D). Therefore, Fab fragments generally are not used in applications that require cell death (eg, cancer immunotherapy). Single-chain variable fragments (scFv) contain a light chain and heavy chain variable region linked together by a peptide. Single-domain antibody (sdAb) has only a light chain variable region or a heavy chain variable region. (Choice A) Antibody fragments pass through the glomerular basement membrane into the collecting system more easily than full immunoglobulins due to their small size; therefore, antibody fragments typically are excreted more (not less) quickly. (Choice E) Because the hypervariable region in a Fab fragment is the same as that in the full immunoglobulin, the fragment and full immunoglobulin bind the antigen with an equivalent affinity. Educational objective: Immunotherapy medications often utilize fragments of a monoclonal immunoglobulin rather than the full immunoglobulin; because fragments are smaller, they typically have better tissue penetration and pharmacokinetics. Fab fragments contain a variable domain and the first constant region from a heavy and light chain; because they do not contain an Fc receptor, Fab fragments cannot trigger cell killing via complement or phagocytosis.

Pharmacology Researchers Develop a Novel Monoclonal Antibody Medication to Treat