Systemic immunotoxin therapy of cancer: advances and prospects

In vivo treatment of Heymann's Nephritis using a cytotoxic protein‐toxin conjugate

“…Immunotoxins have been used in immuno and cancer therapy, and in some cases clinical trials have also begun (reviewed in [19,21,22]). The in vitro and ex vivo use of toxin-antigen conjugates for the therapy of myasthenia gravis, where serum antibodies are formed against the acetylcholine receptor, have also been reported [23,24].…”

Monoclonal antibodies in drug targeting

“…Cancer-cell specific monoclonal antibodies have been raised successfully. Because they have high affinity, monoclonal antibodies, immunoconjugates (containing toxins (5-11), cytotoxic drugs (6,12,13) and radioisotopes (6,(14)(15)(16)(17)) have been investigated extensively in cancer chemotherapy, and some of these conjugates have reached preclinical and also clinical trial stages in the management of colon, breast, skin and bone cancers (10)(11)(12)18).…”

“…The surface bound toxin becomes internalized along with the antibody. In the endosomal compartment, the toxin undergoes processing and the catalytic domain of the toxin is released into the cytosol of the targeted cells, thereby inhibiting protein synthesis and killing the tumour cells (10,11,(85)(86)(87)(88)(89).…”

“…There are several examples of toxicity observed both in laboratory tests and in clinical trials (11). To eliminate this problem, the A chain is enzymatically separated from the toxin before being conjugated with the antibody.…”

“…This approach has led to several immunotoxins which have been shown to be active in vitro. Some have reached Phase I clinical trial in B cell chronic lymphocytic leukaemia, pulmonary, colon, breast and lymph node metastatic melanoma (10,11,(90)(91)(92)(93). In general, major problems with these immunotoxins include undesirable humoral immune responses, instability and reduced therapeutic efficacy due to the large size of the immunotoxin.…”