Antibodies for studying immunotoxin-derived apoptosis

Many of the reagents provided by antibody suppliers are targeted at immunotoxin research. An immunotoxin is a laboratory-synthesized recombinant chimeric protein formed from a targeting domain (e.g a protein or antibody) plus a bacterial or plant toxin such as Pseudomonas or Ricin.

Immunotoxins initiate apoptosis (programmed cell death) and block protein synthesis. They have value as therapeutic tools to kill tumour cells, and their antibodies are used widely in cancer research. The Ricinus Communis Agglutinin 60 Antibody, which can be found on our antibody database, targets a highly toxic protein formed of two disulfide-linked chains. The A-chain is a powerful protein synthesis blocker, one molecule of which can kill a cell, but it requires the B-chain to enter the cell so is not toxic on its own. Researchers can separate the A-chain and use a cleavable bond to link it to an antibody or antigenic protein. The immunotoxin can then be targeted to tumour markers or antibodies on the surface of cancer cells.

Early antibody studies into apoptotic cell death showed a common causer was caspase-induced cleavage of death receptor substrates such as PARP (poly ADP-ribose polymerase, a DNA nick repair enzyme). In breast cancer cells, the pseudomonas endotoxin (PE) induced a five-fold increase in PARP cleavage, probably by caspase-3 activation. Thus immunotoxins acted in two ways: protein synthesis inhibition and apoptotic caspase activation. However, the link between the two processes remained unclear.

More recent research has shown the efficacy of PE/antibody immunotoxins on inhibiting protein synthesis and promoting apoptosis in human breast cancer cell lines. In 2006, Yvonne Andersson et al showed one of these toxins, 425.3PE, induced a stress response leading to hypoxia and an increase in reactive oxygen species (ROS). 425.3PE was shown to initiate a number of signalling events, notably activation of the apoptotic proteins JNK and AMPK. Manipulation of these enzymes may help amplify apoptosis in 425.3PE breast cancer therapy.

Immunotoxin therapies are still largely at the developmental stage. We at Novus Biologicals have an extensive apoptosis antibody catalog, which is proving highly useful to this area of research.

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