20 November 2012

"Mini-cells" against cancer

The founders of the Australian biotech company EnGeneIC, Dr. Himanshu Brahmbhatt and Dr. Jennifer MacDiarmid, have developed "mini-cells" for delivering antitumor drugs directly into tumor cells. Their use will reduce the toxic side effects that develop with the systemic use of chemotherapy.

Mini-cells are miniature bubbles formed from fragments of the cell membrane of mutant bacteria. They can be filled with chemotherapy drugs, and the surface can be coated with antibodies that selectively react with receptors on the surface of tumor cells. The resulting structures selectively interact with cancer cells, avoiding normal cells that do not have corresponding receptors on the surface. Malignant cells recognize mini-cells as bacteria, from the membrane of which they are made, and activate the standard defense mechanism, which consists in absorbing an imaginary bacterium. As a result, the contents of the mini-cell act directly on the nucleus of the tumor cell, destroying it.

The size of the mini-cells is 400 nm, which is much larger than the size of synthetic particles used in the development of drug delivery systems. This size ensures the selective exit of mini-cells from the "leaky" vessels surrounding the tumor, permeated with abnormally large pores, and avoids their accumulation in the liver, intestines and skin and the subsequent development of undesirable side effects.

Experiments on cell cultures and laboratory animals have already demonstrated the ability of mini-cells to perform their functions, so the recently published results of a clinical study are a real breakthrough in the development of this fundamentally new direction.

As part of a clinical study, scientists loaded mini-cells with cytotoxic chemotherapy drug paclitaxel, currently used for the treatment of various malignant tumors, and coated them with antibodies selectively binding to the protein receptor for epidermal growth factor expressed by many cancer cells. The study was planned as a standard phase I clinical trial, the purpose of which was to assess the safety and toxicity of mini-cells by administering progressively increased doses of mini-cells to a small group of patients and carefully monitoring the safety of therapy and toxic effects at the body level.

A total of 28 patients from four Australian cancer centers who had the last stages of tumors incurable with traditional therapeutic approaches participated in the study. In 10 patients who received more than one injection of mini-cells, the condition remained stable for at least six weeks.

According to the authors, the main result of the study is a demonstration of the safety of introducing mini-cells to patients with the last stages of cancer. Additionally, the possibility of repeated administration of the drug was shown. One of the patients received 45 injections within 15 months. The most serious manifestation of toxicity was the development of a moderate rash on the day of administration. All manifestations of side effects disappeared within a week. The introduction of the highest dosages was accompanied by additional side effects, in particular, changes in the results of liver functional tests, due to which, despite their asymptomatic nature, the dose increase was discontinued.

Currently, it is planned to conduct phase II clinical trials, including studies involving patients with glioblastoma, who will be injected with mini-cells loaded with doxorubicin. The researchers also plan to develop imaging techniques to track the movement of mini-cells in the body.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of The European CanCer Organization:
First trial in humans of “minicells”: a completely new way of delivering anti-cancer drugs.


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