Monoclonal Antibody Therapies for Cancer

Study Notes

Monoclonal antibodies are produced by a single clone of B lymphocytes, targeting a single epitope.
Originally generated by fusing antigen-specific cells to myeloma cells, now often using recombinant techniques for amplification of heavy and light chains.
Antibodies have variable regions (Fv) and constant regions (Fc) for antigen binding and effector functions, respectively.
Therapeutic strategies use monoclonal antibodies to block signals, stimulate internalization, or trigger apoptosis.
Examples include Trastuzumab (HER2 targeting) and Rituximab (CD20 targeting).
Antibody-drug conjugates (ADCs) combine antibodies with toxins or chemotherapeutic drugs for targeted delivery.
Radiolabelled antibodies use radioactive isotopes to destroy tumour cells.
Bispecific monoclonal antibodies, binding to two different targets, can engage effector cells (T cells) in cancer cell destruction.
HER2 receptors, overexpressed in some breast cancers, are targeted for dimerization inhibition.
Trastuzumab inhibits HER2 signalling, and Pertuzumab blocks dimerization to further target HER2 overexpressing breast cancers.

HER2 is a transmembrane receptor tyrosine kinase, often overexpressed in breast cancer.
HER2 can dimerize with other HER family members (e.g., EGFR and HER3), increasing its activity.
Trastuzumab enhances receptor internalization and reduces HER2-mediated signalling.
Pertuzumab inhibits HER2 dimerization.

PSMA (prostate-specific membrane antigen) is a target for prostate cancer.
Monoclonal antibodies tagged with Lutetium-177 (a radioactive isotope) can be used.
This treatment delivers a destructive dose of radiation to targeted prostate cancer cells.

These antibodies target two different antigens.
The "knobs into holes" strategy describes how these antibodies bind to specific receptors.
Bispecific antibodies can be used to target effector cells (e.g., T cells) to cancer cells, improving treatment efficacy.

CD47 is a cell surface receptor that interacts with SIRPa on macrophages.
CD47-blocking antibodies remove the "don't eat me" signal for macrophages, enabling them to phagocytose tumor cells.

Single-domain antibody fragments derived from Camelids (camels, llamas, and alpacas).
Sharks also produce nanobodies.
Smaller and more stable than conventional antibodies.

Bispecific antibodies that engage T cells with cancer cells for enhanced cell killing.
Example, Blinatumomab targets CD19 and CD3 to induce T cell mediated lysis of B-cell malignancies.