Monoclonal Antibody Therapies for Cancer

Study Notes

Monoclonal antibodies are produced by a single clone of B lymphocytes, targeting a single epitope.
Initially generated by fusing antigen-specific cells with myeloma cells, but now often amplified via recombinant techniques.
Antibodies have variable and constant regions; the variable region (Fv) binds to the antigen, while the constant region (Fc) interacts with other parts of the immune system.

Blocking Signals: Techniques like Trastuzumab and Pertuzumab can block signals or stimulate internalization and apoptosis.
Antibody-Drug Conjugates (ADCs): Attaching drugs to antibodies, like Trastuzumab-deruxtecan or Trastuzumab-emtansine, targets cancer cells for death.
Radiolabeled Antibodies: Attaching radioactive isotopes, such as Lutetium-177, to antibodies directs radiation to cancer cells.
Bispecific Antibodies: These antibodies bind to two different targets, like a cancer cell receptor and a T cell receptor, enabling T cells to attack the cancer cells.
- Examples include CD3 and CD20 bispecifics, CD3 and PSMA bispecifics, and CD3 and HER2 bispecifics.

HER2 is a receptor involved in cell growth, commonly overexpressed in breast cancer.
Trastuzumab enhances HER2 receptor internalization and weakens signalling, while Pertuzumab hinders dimerization of HER2 receptors.
Overexpression of HER2 in tumours often means the receptors are dimerized more frequently, increasing cancer cell growth

CD47 is a cell surface protein that often overexpresses in tumors, typically triggering a "don't-eat-me" signal for macrophages to prevent their engulfment and destruction.
Targeting CD47 with monoclonal antibodies can eliminate this signal, enabling macrophages to phagocytose the cancer cells.

PSMA is a protein expressed on prostate cancer cells.
Radiolabeled monoclonal antibodies (like those tagged with Lutetium-177) can target PSMA and deliver targeted radiation to kill prostate cancer cells.

Direct Killing: Monoclonal antibodies can directly trigger apoptosis in cancer cells.
Complement-Dependent Cytotoxicity (CDC): The complement system can be activated by antibody binding to cancer cells to lead to their lysis.
Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC): Certain immune cells (NK cells) can be activated by antibody-bound cancer cells, causing the release of enzymes to kill them.
Antibody-Dependent Phagocytosis (ADP): Recognition by macrophages via antibody-bound targets, leading to phagocytosis (cellular destruction).

BiTEs are antibodies that bind to both a cancer cell-surface target and a T-cell receptor, enabling T cells to effectively kill the targeted cancer cells.
Blinatumomab is an example.

mRNA-based vaccines and nanobodies are innovative approaches.
Nanobodies are smaller than conventional antibodies and can be used in therapies.

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