Affinity and avidity in antibody-based tumor targeting.

Area of Science:

• Immunology
• Pharmacology
• Biochemistry

Background:

• Successful tumor targeting by antibodies depends on tumor properties, antibody pharmacology, and antibody-antigen interactions.
• Antibody affinity and avidity are critical factors influencing tumor penetration, cellular internalization, catabolism, specificity, and overall efficacy.

Purpose of the Study:

• To review principles guiding models for predicting antibody tumor penetration and cellular internalization.
• To critically overview experimental studies on the role of affinity and avidity in antibody-mediated tumor targeting.

Main Methods:

• Review of existing literature and theoretical models.
• Analysis of experimental studies investigating antibody-antigen binding dynamics in tumor models.

Main Results:

• Antibody binding affinity influences localization within tumors, affecting perivascular space concentration versus diffusion.
• Slow dissociation rates can complicate antibody distribution due to antigen binding, internalization, and degradation.
• Increased avidity and broader specificity offer improved tumor targeting compared to solely increasing affinity.

Conclusions:

• Antibody-antigen binding dynamics, particularly affinity and avidity, are crucial for effective tumor targeting.
• Optimizing antibody avidity and specificity, rather than just affinity, is a promising strategy for enhancing therapeutic outcomes.