Monoclonal Antibody Therapies: Mechanisms and Targets

In course

Description

This lecture covers the use of monoclonal antibodies in cancer treatment, focusing on targeting specific antigens and immunosuppressive mechanisms. It explains how antibodies like Herceptin and Rituximab work, as well as newer immune checkpoint inhibitors like CTLA-4 and PD-1. The instructor details the mechanisms of action of these antibodies, including activating immune responses, blocking immunosuppression, and inducing cytotoxic effects. The lecture also discusses the role of Tregs and CD8 T cells in tumor-associated immunosuppression, emphasizing the importance of understanding these interactions for developing effective therapies.

In MOOCs (4)

Instructors (2)

Official source

https://mediaspace.epfl.ch/media/0_dm1nqqc3

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Related concepts (23)

A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies can have monovalent affinity, binding only to the same epitope (the part of an antigen that is recognized by the antibody). In contrast, polyclonal antibodies bind to multiple epitopes and are usually made by several different antibody-secreting plasma cell lineages.

Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other conditions. In general, deliberately induced immunosuppression is performed to prevent the body from rejecting an organ transplant.

In biology, chimeric antigen receptors (CARs)—also known as chimeric immunoreceptors, chimeric T cell receptors or artificial T cell receptors—are receptor proteins that have been engineered to give T cells the new ability to target a specific antigen. The receptors are chimeric in that they combine both antigen-binding and T cell activating functions into a single receptor. CAR T cell therapy uses T cells engineered with CARs to treat cancer.

CD8 (cluster of differentiation 8) is a transmembrane glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). Along with the TCR, the CD8 co-receptor plays a role in T cell signaling and aiding with cytotoxic T cell-antigen interactions. Like the TCR, CD8 binds to a major histocompatibility complex (MHC) molecule, but is specific for the MHC class I protein. There are two isoforms of the protein, alpha and beta, each encoded by a different gene. In humans, both genes are located on chromosome 2 in position 2p12.

Tumor antigen is an antigenic substance produced in tumor cells, i.e., it triggers an immune response in the host. Tumor antigens are useful tumor markers in identifying tumor cells with diagnostic tests and are potential candidates for use in cancer therapy. The field of cancer immunology studies such topics. Normal proteins in the body are not antigenic because of self-tolerance, a process in which self-reacting cytotoxic T lymphocytes (CTLs) and autoantibody-producing B lymphocytes are culled "centrally" in primary lymphatic tissue (BM) and "peripherally" in secondary lymphatic tissue (mostly thymus for T-cells and spleen/lymph nodes for B cells).