Human toxin-based recombinant immunotoxins/chimeric proteins as a drug delivery system for targeted treatment of human diseases

Abstract

Human toxin-based immunotoxins/chimeric proteins for the targeted delivery of drugs are still in their early stages of development. However, they are certain to advance in the very near future to become an extra weapon in the everlasting war against human diseases, mainly cancer.

Selective killing of Kaposi's sarcoma-associated herpesvirus lytically infected cells with a recombinant immunotoxin targeting the viral gpK8.1A envelope glycoprotein

“…88 The immunogenicity problem is being addressed by identifying and eliminating B cell epitopes using site-directed mutagenesis 89 or by choosing human-derived proteins as the cytotoxic moieties. 90,91 In considering the application of any of these specific cell-killing modalities, treatment of viral infections has the advantage of targeting a viral-encoded antigen, thereby avoiding side-effects frequently encountered in cancer therapy owing to killing of normal cells expressing the targeted human antigen; on the other hand, a single virus-infected cell MCD patients; the results were interpreted as reflecting mainly (in addition to the possible direct anti-KSHV activity of valganciclovir) the ability of the products of the KSHV genes ORF21 (encoding thymidine kinase) and ORF36 (encoding a phosphotransferase) to activate the conversion of zidovudine and ganciclovir, respectively, into cytotoxic compounds. The efficacy was thus considered to be an example of "virus-activated cytotoxic therapy."…”

Learning from the past: historical aspects of bacterial toxins as pharmaceuticals

“…On the basis of this, many other bacterial toxins have also been suggested for use as pharmaceuticals, and only a few recent examples are listed here [33][34][35][36]. Toxins secreted from bacteria such as methicillin resistant Staphyloccocus aureus (MRSA) are a promising tool in the defense against themselves, by utilizing their ability to 'punch holes' into specially engineered liposomes that carry antibiotics directed at the toxin producing bacteria [37].…”

Engineered Versions of Granzyme B and Angiogenin Overcome Intrinsic Resistance to Apoptosis Mediated by Human Cytolytic Fusion Proteins

“…Further examples of human effector domains include death receptor ligands and pro-apoptotic members of the BCL-2 family [16,28]. Several hCFPs have already been tested to confirm their selective activity and efficiency in vitro and in vivo [16,29].…”