Activated protein kinase C (PKC) contributes to tumor survival and proliferation, provoking the development of inhibitory agents as potential cancer therapeutics. Immunotoxins are antibody-based recombinant proteins that employ antibody fragments for cancer targeting and bacterial toxins as the cytotoxic agent. Pseudomonas exotoxin-based immunotoxins act via the ADP-ribosylation of EF2 leading ...

A plant single-chain ribosome-inactivating protein derived from the root tuber of Trichosanthes kirilowii, termed trichosanthin (TCS), was modified with 2-iminothiolane. It was not like trichokirin, a ribosome-inactivating protein derived from the seeds of the same plant, in that TCS retained full activity when 1.5 sulfhydryl groups were introduced into each TCS molecule by 2-iminothiolane modi...

Introduction Antibodies to cytotoxic T-lymphocyte-associated protein 4 (CTLA4) potentiate an immune response against cancer. Response rates in melanoma patients are range from 10 to 19%[1]. To increase the efficacy and variety of cancer types treated by anti CTLA4, a combination therapy should be pursued. RG7787 is a recombinant immunotoxin composed of an anti-mesothelin Fab fused to a fragment...

Immunotoxins are hybrid proteins composed of peptide cytotoxins covalently linked to target cell-selective peptide ligands such as monoclonal antibodies, antibody fragments, growth factors, or cytokines. Immunotoxins have been synthesized that kill cells selectively in tissue culture with great potency and have excellent in vivo efficacy with short treatment courses in immunocompromised rodents...

Impaired apoptosis is often a key element in tumor development. Therefore, drugs mimicking prosurvival antagonists offer promise as cancer therapeutics. When ABT-737, a BH3-only mimetic, was added to KB3-1 human cervical adenocarcinoma cells,we noted an induction of an endoplasmic reticulum (ER) stress response and the dislocation of ER luminal proteins, including chaperones, to the cell cytoso...

We developed a model to assess the therapeutic effects of the 45-2D9-ricin A-chain immunotoxin (RTA) on pulmonary metastases. The 45-2D9 mouse monoclonal antibody recognizes a Mr 74,000 glycoprotein highly expressed by rat fibroblasts transformed with the Kirsten sarcoma virus (transformed rat fibroblasts). These cells metastasize spontaneously and form lung colonies in nu/nu and irradiated BAL...

T101-ricin A-chain immunotoxin is a hybrid molecule made up of the T101 monoclonal antibody bound to the A-chain of ricin. It specifically destroys cells expressing the cell surface T65 antigen. We have designed a preclinical study to evaluate its possible use for the in vitro treatment of T-cell hematological cancers prior to autologous bone marrow transplantation. The data presented here show...

An immunotoxin conjugate of a murine monoclonal antibody against human transferrin receptors and the A chain of ricin was examined for its potential to inhibit selectively the growth of retinal pigment epithelial (RPE) cells which grow in an uncontrolled manner in proliferative vitreoretinopathy. The probable efficacy of such an agent in vivo stems from the observation that actively proliferati...

The ability to target proliferating cells is important for agents used to modulate wound healing by decreasing the growth of fibroblasts. Proliferating cells are known to express increased numbers of transferrin receptors and have increased receptor turnover. 454A12 Mab-rRA, an immunotoxin containing anti-human transferrin receptor monoclonal antibody conjugated to recombinant ricin A chain, wa...

Immunotoxins are chimeric proteins comprising a specific cellular targeting domain linked to a cytotoxic factor. Here we describe the design and use of a novel, peptide-based immunotoxin that can initiate selective cytotoxicity on ErbB2-positive cells. ErbB2 is a receptor tyrosine kinase that is overexpressed in the tumor cells of approximately 30% of breast cancer patients. Immunotoxin candida...