Immunogenicity and Pharmacokinetics of Therapeutic Antibodies

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Questions and Answers

What is the purpose of PEGylation in immunogenicity?

To enhance the immunogenicity of a protein
To shield the antigen from being recognized as immunogenic (correct)
To reduce the effectiveness of monoclonal antibodies
To increase the size of the protein

What is the main challenge in the pharmacokinetics of monoclonal antibodies?

Protein degradation
Polyethylene glycol interference
B cell fusion
Passage in tissues (correct)

What type of monoclonal antibodies is no longer used for therapeutic purposes?

Mouse monoclonal antibodies (correct)
Polyclonal antibodies
Human monoclonal antibodies
Humanized monoclonal antibodies

What is the purpose of the hybridoma technique in monoclonal antibody production?

To fuse B cells with myeloma cell lines (A) Signup and view all the answers

What is the function of polyethylene glycol (PEG) in the hybridoma technique?

To allow the fusion of B cells with myeloma cell lines (C) Signup and view all the answers

What is the medium used to select correctly fused cells in the hybridoma technique?

HAT medium (A) Signup and view all the answers

Why do B cells die in the hybridoma technique?

Because of their short life-span (A) Signup and view all the answers

What is the advantage of humanized or human monoclonal antibodies over mouse monoclonal antibodies?

They are better for therapeutic purposes (B) Signup and view all the answers

Which type of monoclonal antibody has the lowest immunogenicity?

Human antibodies (-umab) (D) Signup and view all the answers

What is the primary reason why murine monoclonal antibodies (-omab) were abandoned as drugs?

They were highly immunogenic. (A) Signup and view all the answers

What is the main difference between chimeric antibodies (-ximab) and humanized antibodies (-zumab)?

Humanized antibodies have a higher percentage of human sequences. (C) Signup and view all the answers

What does the term "anti-drug antibodies" (ADAs) refer to?

Antibodies produced by the body that target and neutralize the therapeutic antibody. (A) Signup and view all the answers

Which of the following is NOT a characteristic of monoclonal antibodies?

They are typically synthesized by bacteria or yeast cells. (B) Signup and view all the answers

How can therapeutic antibodies be used to treat autoimmune disorders?

By suppressing the immune system to prevent it from attacking healthy tissues. (D) Signup and view all the answers

What can occur if a patient develops antibodies against a medication?

The drug cannot be used anymore in that patient. (D) Signup and view all the answers

Which factor is NOT mentioned as affecting the immunogenicity of protein drugs?

The age of the patient. (A) Signup and view all the answers

Which situation could lead to antibody production that cross-reacts with endogenous proteins?

Using a protein drug with structural similarities to the body's own proteins. (B) Signup and view all the answers

Patients with what condition may be more prone to developing antibodies against self-antigens?

Autoimmune diseases. (C) Signup and view all the answers

The immunogenicity of a protein drug could potentially be lower when the drug is administered how?

Once a month. (D) Signup and view all the answers

What type of reaction could occur in a patient as a result of protein drug administration?

Anaphylaxis. (A) Signup and view all the answers

Study Notes

Immunogenicity and Modification of Therapeutic Antibodies

PEGylation involves attaching polyethylene glycol (PEG) to proteins to shield them from immune recognition, reducing immunogenicity.

Pharmacokinetics of Monoclonal Antibodies (mAb)

Monoclonal antibodies share pharmacokinetic properties with protein drugs, with the primary challenge being tissue penetration due to their size.

Production Techniques

The hybridoma technique, developed in the 1970s, involves immunizing mice with target antigens to create mouse mAbs.
B cells producing antibodies are fused with myeloma cells using PEG to allow continuous duplication.
Selection of successfully fused cells occurs in HAT medium, where only hybrid cells survive due to their enzymatic capability.

Immunogenicity and Patient Response

Administration of therapeutic antibodies can elicit the formation of anti-drug antibodies (ADAs), which may neutralize treatment efficacy.
Immunogenicity is influenced by drug administration frequency; less frequent dosing may lead to lower antibody development.
Potential adverse reactions include anaphylaxis and cross-reactivity, especially if the therapeutic protein resembles endogenous proteins.

Genetic Factors and Autoimmunity

Patients with autoimmune conditions may have heightened susceptibility to developing antibodies against self-antigens due to impaired immune regulation.

Types of Monoclonal Antibodies

Mouse monoclonal antibodies (suffix -omab) are highly immunogenic and largely replaced in therapeutic use.
Chimeric antibodies (suffix -ximab) have a human constant region but retain 33% murine variable regions, reducing but not eliminating immunogenicity.
Humanized antibodies (suffix -zumab) contain only 5-10% murine sequences, resulting in significantly lower immunogenicity.
Fully human antibodies (suffix -umab) have minimal or no murine content, offering the lowest immunogenic profiles.

Conclusion on Antibody Immunogenicity

Regardless of the type, all therapeutic monoclonal antibodies can induce ADA responses to varying extents, impacting clinical effectiveness.

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Description

This quiz covers the reduction of immunogenicity through PEGylation and the pharmacokinetics of monoclonal antibodies, comparing them to protein drugs.