Antibody-Based Immunotoxins for the Treatment of Cancer

Abstract

Antibody-based immunotoxins comprise an important group in targeted cancer therapeutics. These chimeric proteins are a form of biological guided missiles that combine a targeting moiety with a potent effector molecule. The targeting moiety is mostly a monoclonal antibody (MAb) or a recombinant antibody-based fragment that confers target specificity to the immunotoxin. The effector domain is a potent protein toxin of bacterial or plant origin, which, following binding to the target cells, undergoes internalization and causes cell death. Over time and following research progression, immunotoxins become better fitted to their purpose, losing immunogenic fragments and non-specific targeting moieties. Many immunotoxins have gone through clinical evaluation. Some of these have been shown to be active and work is progressing with them in the form of further clinical trials. Others, mostly developed in the previous century, failed to generate a response in patients, or even caused undesired side effects. This article reviews the antibody and protein-toxin based immunotoxins that were clinically evaluated up to the present day.

Pseudomonas aeruginosa exotoxin T induces potent cytotoxicity against a variety of murine and human cancer cell lines

“…There are multiple approaches that have been or are currently being investigated in several clinical trials that may accomplish this task. One approach is conjugation with tumour-specific antibodies (reviewed by Becker & Benhar, 2012). Conjugating ExoT to tumourspecific antibodies or the immunoglobulin variable fragment regions can enhance the delivery of the toxin (e.g.…”

“…For example, Pseudomonas exotoxin A and diphtheria toxin are the most common bacterial toxins that have been or are currently under clinical evaluation against a variety of haematologic malignancies and solid tumours with promising results (reviewed by Becker & Benhar, 2012). Although these new recombinant immunotoxins have shown high potency in killing tumour cells with high specificity, they too share the limitation of targeting a single cellular substrate, eEF-2 (Jørgensen et al, 2008).…”

Improving the Therapeutic Potential of Human Granzyme B for Targeted Cancer Therapy

“…First-generation ITs have shown promising results in in vitro studies and preclinical tests [18][19][20][21][22][23][24][25][26][27][28] and have also been tested in a small number of clinical trials [29,30]. The most prominent example is a recombinant IT comprising the diphtheria toxin and interleukin-2, which has been approved by the FDA for the treatment of T-cell lymphoma [31].…”

Immunotoxin: A new tool for cancer therapy

“…OVB3-PE and 260F9-rRTA) often cause severe side effects that, in many cases, are not followed in the late stages of clinical treatment. 92 LMB-2 was evaluated in a phase-I study completed in 2011 and applied in patients with hematologic malignancies; of 35 patients, complete response (CR) has been found in 1 patient, while partial response (PR) showed in 7 patients with a total response rate of 24%. 92 In 2001, initial approval of DD for treatment of cutaneous T-cell lymphoma (CTCL) was granted by the FDA.…”