Topic 10.1 - part 6 - Case Study- HUMIRA (3.52 min)

Discovery and Approval of Humira

  • Humira Overview

    • First human antibody approved by the FDA in 2002.

    • Type: Recombinant monoclonal antibody; produced in cells.

Mechanism of Action

  • Target: Directed against TNF (tumor necrosis factor alpha).

    • Role of TNF-alpha:

      • A cytokine involved in inflammatory processes.

      • Used in conditions like psoriasis, ulcerative colitis, and arthritis.

    • Dosage Advantage:

      • Administered via injection once every two weeks.

      • Long half-life of antibodies enhances efficacy.

Interaction with Immune System

  • Production of TNF-alpha:

    • Secreted by T cells; interacts with macrophage receptors.

    • Two receptors involved: p55 (TNF receptor 1) and p75 (TNF receptor 2).

  • Inflammation Process:

    • Activation of macrophages leads to the release of interleukins.

    • Results in inflammation within the synovial membrane of joints (e.g., knee).

  • Role of Humira:

    • Sequesters TNF-alpha to prevent it from binding to its receptors, halting the inflammatory response.

Production Process of Humira

  • Engineering the Antibody:

    • Uses the sequence of two genes coding for the antibody, focusing on variable regions.

    • The variable regions are optimized using phage display technology.

      • Panning method selects effective regions that recognize TNF-alpha.

  • Selection and Expression:

    • Selected sequences are integrated into the genome of Chinese hamster ovary (CHO) cells.

    • CHO cells express the antibody naturally as they produce normal proteins.

  • Final Outcome:

    • Resulting in the production of the therapeutic antibody, Humira.