‘Drug Factory’ Implants Could Eliminate Specific Lung Cancer

Rice University and Baylor College of Medicine researchers have shown they can seradicate advanced-stage mesothelioma tumor in mice in just a few days with a treatment combining Rice’s cytokinedrug factoryimplants and a checkpoint inhibitor drug.

The researchers administered the drug-producing beads, which are no larger than the head of a pin, next to tumors where they could produce continuous, high doses of interleukin-2 (IL-2), a natural compound that activates white blood cells to fight cancer. The study, published online today in Clinical Cancer Research, is the latest in a string of successes for the drug-factory technology invented in the lab of Rice bioengineer Omid Veiseh, including Food and Drug Administration (FDAapproval to begin clinical trials of the technology this fall in ovarian cancer patients.

From the beginning, our objective was to develop a platform therapy that can be used for multiple different types of immune system disorders or different types of cancers,” said Rice graduate student Amanda Nash, who spent several years developing the implant technology with study co-lead author Samira Aghlara-Fotovat, a fellow student in Veiseh’s lab.

The cytokine factories consist of alginate beads loaded with tens of thousands of cells that are genetically engineered to produce natural IL-2, one of two cytokines the FDA has approved for treatment of cancer. The factories are just 1.5 millimeters wide and can be implanted with minimally invasive surgery to deliver high doses of IL-2 directly to tumors. In the mesothelioma study, the beads were placed beside tumors and inside the thin layer of tissue known as the pleura, which covers the lungs and lines the interior wall of the chest.

I take care of patients who have malignant pleural mesothelioma,” said Dr. Bryan Burt, professor and chief of Baylor’s Division of Thoracic Surgery in the Michael E. DeBakey Department of Surgery. “This is a very aggressive malignancy of the lining of the lungs. And it’s very hard to treat completely by surgical resection. In other words, there is often residual disease that is left behind. The treatment of this residual disease with local immunotherapy — the local delivery of relatively high doses of immunotherapy to that pleural space — is a very attractive way to treat this disease.”

Veiseh said the mesothelioma study began when Burt and Baylor surgeon and associate professor Dr. Ravi Ghanta heard about the early results of ovarian cancer animal tests Veiseh’s team was conducting with collaborators at the University of Texas MD Anderson Cancer Center. In March, Veiseh and MD Anderson collaborators published a study showing IL-2-producing beads could eradicate advanced-stage ovarian and colorectal tumors in mice in less than a week.

They were really impressed by the preclinical data we had in ovarian cancer,” Veiseh said of Burt and Ghanta. “And they asked the question, ‘Could we actually leverage the same system for mesothelioma?’

Source: https://blogs.bcm.edu/

Blood Vessels Can Contribute To Tumor Suppression

A study from the Institute of Pharmacology and Structural Biology in Toulouse (France) has introduced a novel concept in cancer biology : Blood vessels in human tumors are not all the same and some types of blood vessels found in the tumor microenvironment (i. e. HEVs) can contribute to tumor suppression rather than tumor growth(Cancer Res 2011).

 A better understanding of HEVs at the molecular level, which is one of the major objectives of the research team, may have an important impact for cancer therapy.

Dendritic cells, which are well known for their role as antigen-presenting cells, play an unexpected and important role in the maintenance of HEV blood vessels in lymph nodes (Nature 2011). In addition, the scientists discovered the frequent presence of HEVs in human solid tumors, and their association with cytotoxic lymphocyte infiltration and favourable clinical outcome in breast cancer. They also showed that IL-33 is a chromatin-associated cytokine (PNAS 2007, 453 citations) that function as an alarm signal (alarmin) released upon cellular damage (PNAS 2009, 312 citations). Inflammatory proteases can generate truncated forms of IL-33 that are 30-fold more potent than the full length protein for activation of group 2 innate lymphoid cells (PNAS 2012, 133 citations, PNAS 2014).

An important objective  is now to further characterize IL-33 regulation and mechanisms of action in vivo, through the use of multidisciplinary approaches.

Source: http://www.ipbs.fr/