The development of immunoconjugates for targeted cancer therapy

Abstract

Immunoconjugates are specific, highly effective, minimally toxic anticancer therapies that are beginning to show promise in the clinic. Immunoconjugates consist of three separate components: an antibody that binds to a cancer cell antigen with high specificity, an effector molecule that has a high capacity to kill the cancer cell, and a linker that will ensure the effector does not separate from the antibody during transit and will reliably release the effector to the cancer cell or tumour stroma. The high affinity antibody–antigen interaction allows specific and selective delivery of a range of effectors, including pharmacologic agents, radioisotopes, and toxins, to cancer cells. Some anticancer molecules are not well tolerated when administered systemically owing to unacceptable toxicity to the host. However, this limitation can be overcome through the linking of such cytotoxins to specific antibodies, which mask the toxic effects of the drug until it reaches its target. Conversely, many unconjugated antibodies are highly specific for a cancer target, but have low therapeutic potential and can be repurposed as delivery vehicles for highly potent effectors. In this Review, we summarize the successes and shortcomings of immunoconjugates, and discuss the future potential for the development of these therapies.

PU-H71: An improvement on nature's solutions to oncogenic Hsp90 addiction

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Targeting carbonic anhydrase IX with small organic ligands

“…Current using a ligand of an accessible tumor antigen to selectively transport toxins into antigen-expressing neoplastic lesions, the therapeutic efficacy of cell-killing agents can be increased whilst reducing their side effects [34,35].…”

“…As an alternative to direct inhibition approaches, the highaffinity interaction of CAIX ligands with their cognate target can be exploited for the targeted delivery of potent cytotoxic drugs into solid tumors [34,35]. Clinically used cytotoxic drugs in their 'naked' form often do not reach solid tumors in high quantities but accumulate in healthy organs [36], where they can cause severe side effects.…”

Keratinocyte growth factor receptor: a therapeutic target in solid cancer

“…Thus, development of novel treatment options is desperately needed. Based on the knowledge of molecular and genetic changes in the development of solid cancer, the molecular targeting agents have been found critical for cancer therapy [1]. Recently, some studies have shown that keratinocyte growth factor receptor (KGFR) is important for cancer therapy [2].…”