Molecular immunotherapy is the use of antibodies or antibody fragments to target and destroy cancer cells in patients. These targeting molecules, called immunotoxins, are a form of antibody-based therapeutics that have been shown to be an effective cancer treatment. Immunotoxins typically target and kill cells by binding to a target cell-specific ligand and then delivering a cytotoxic agent to the cell. Unfortunately, a major problem in the clinical application of immunotoxins is the lack of specificity; non-target cells are also killed when the immunotoxin is delivered to the cell. This non-specific delivery results in high doses of the toxic agent being delivered to healthy tissue, which can cause severe side-effects. In fact, many clinical trials using immunotoxins are stopped before completion because of the unacceptable side-effects.
Immunotoxins are prepared by linking immunotoxin components to a targeting ligand that binds specifically to cancer cells. Several different targeting ligands have been developed, including peptides and antibodies. The choice of targeting ligand determines which cells the immunotoxin will bind and subsequently kill. Most targeting ligands, including peptides and antibodies, are synthesized chemically, but bacteriophage-derived peptides have emerged as a new class of targeting ligands. The great advantage of the bacteriophage approach is that the peptides are encoded in a virus's own DNA, which eliminates the need for chemical synthesis.
A major problem with the production of immunotoxins is the need for a complex purification process. In a typical production procedure, the toxic agent is linked to the targeting ligand using heterobifunctional cross-linking reagents that allow the toxic and targeting ligands to be purified simultaneously. In addition, the heterobifunctional cross-linking reagents and toxic agent must be purified to avoid toxicity to the host. Thus, purification of the targeting ligand and toxic agent is one of the most time-consuming steps in the preparation of immunotoxins. In a typical purification process, a bacteriophage displaying the targeting ligand is incubated with a cell suspension. The cells are lysed, and the immunotoxin-containing lysate is isolated. The isolated lysate is then treated with a ligand purification resin, where the targeting ligand binds. After washing, the immunotoxin is eluted from the resin and further purified.
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