‘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/

AI-designed Antibody Enters Clinical Trials

The Israeli company Biolojic Design will conduct a trial for cancer patients in Australia with a new type of drugAulos Biosciences is now recruiting cancer patients to try it’s world’s first antibody drug designed by a computer. The computationally designed antibody, known as AU-007, was planned by the artificial intelligence platform of Israeli biotech company Biolojic Design from Rehovot, in a way that would target a protein in the human body known as interleukin-2 (IL-2). The goal is for the IL-2 pathway to activate the body’s immune system and attack the tumors.

The clinical trial will be conducted on patients with final stage solid tumors and will last about a year – but the company hopes to present interim results during 2022. The trial has raised great hopes because if it is successful, it will pave the way for the development of a new type of drug using computational biology and “big data.” Aulos presented pre-clinical data from a study on 19 mice – and they all responded positively to the treatment. In the 17-day trial period of the study, the antibody led to the complete elimination of the tumors in 10 of the mice – and to a significant delay in the development of the tumors in the other nine mice.

Aulos was founded in Boston as a spin-off of Biolojic and venture capital firm Apple Tree Partners, which invested $40 million in the company to advance the antibody project and prove its clinical feasibility. Drugs based on antibodies are considered to be one of the greatest hopes for anti-cancer solutions. Among the best-known in the field are Keytruda, mostly used to treat melanomas and lung cancer; and Herceptin for breast cancer. But the antibodies given today to cancer patients are created by a method that also has disadvantages – most are produced by the immune system in mice, and then are replicated to enable mass production.

Source: https://www.haaretz.com/

‘Drug Factory’ Implants Could Eliminate Cancer

Rice University bioengineers have shown they can eradicate advanced-stage ovarian and colorectal cancer in mice in as little as six days with a treatment that could be ready for human clinical trials later this year. The researchers used implantabledrug factories” the size of a pinhead to deliver continuous, high doses of interleukin-2, a natural compound that activates white blood cells to fight cancer. The drug-producing beads can be implanted with minimally invasive surgery. Each contains cells engineered to produce interleukin-2 that are encased in a protective shell.

The treatment and animal test results are described online today in a Science Advances study co-authored by Omid VeisehAmanda Nash and colleagues from Rice, the University of Texas MD Anderson Cancer Center, the University of Virginia and others.

Veiseh, an assistant professor of bioengineering whose lab produced the treatment, said human clinical trials could begin as soon as this fall because one of his team’s key design criteria was helping cancer patients as quickly as possible. The team chose only components that had previously proven safe for use in humans, and it has demonstrated the safety of the new treatment in multiple tests.

Rice University bioengineers Amanda Nash (left) and Omid Veiseh with vials of bead-like “drug factories” they created to treat cancer. The beads are designed to continuously produce natural compounds that program the immune system to attack tumors. 

We just administer once, but the drug factories keep making the dose every day, where it’s needed until the cancer is eliminated,” Veiseh said. “Once we determined the correct dose — how many factories we needed — we were able to eradicate tumors in 100% of animals with ovarian cancer and in seven of eight animals with colorectal cancer.”

In the newly published study, researchers placed drug-producing beads beside tumors and within the peritoneum, a sac-like lining that supports intestines, ovaries and other abdominal organs. Placement within this cavity concentrated interleukin-2 within tumors and limited exposure elsewhere. “A major challenge in the field of immunotherapy is to increase tumor inflammation and anti-tumor immunity while avoiding systemic side effects of cytokines and other pro-inflammatory drugs,” said study co-author Dr. Amir Jazaeri, professor of gynecologic oncology and reproductive medicine at MD Anderson. “In this study, we demonstrated that the ‘drug factories’ allow regulatable local administration of interleukin-2 and eradication of tumor in several mouse models, which is very exciting. This provides a strong rationale for clinical testing.

Source: https://news.rice.edu/

Nanoparticles Act As Immunotherapy Agents

University of Wisconsin–Madison researchers have developed nanoparticles that, in the lab, can activate immune responses to cancer cells. If they are shown to work as well in the body as they do in the lab, the nanoparticles might provide an effective and more affordable way to fight cancer.

They are cheaper to produce and easier to engineer than the antibodies that underlie current immunotherapies, which as drugs cost tens of thousands of dollars a month.

The nanoparticles were made of sections of the T cell protein PD-1 (in blue) attached to a branched core called a dendrimer (in gray). The branches in the core of the nanoparticle allowed many chunks of the PD-1 protein to bind to the nanoparticle, increasing its effectiveness.

Immunotherapy basically boosts the patient’s own immune system to fight against cancer cells better,” says Seungpyo Hong, a professor in the UW–Madison School of Pharmacy. “The antibodies that are used right now are large, they’re expensive, they’re hard to engineer, and they don’t always show the highest level of efficacy either. So we wanted to explore other ways to activate the immune system.

Hong and postdoctoral associate Woo-jin Jeong led the study, published online Jan. 2 in the Journal of the American Chemical Society, with collaborators at the University of Illinois at Chicago. It’s the first demonstration that nanoparticles can act as immunotherapy agents.

More research is needed to understand their effectiveness in the body, but Hong has applied for a patent on the new nanoparticles and is now testing them in animal models.

In tests against lab-grown strains of cancer, the nanoparticles boosted production of the immune stimulating protein interleukin-2 by T cells, one kind of immune cell in the body, by about 50 percent compared to no treatment. They were just as effective as antibodies. The nanoparticles were also able to improve the effectiveness of the chemotherapy drug doxorubicin in similar tests.

Normally, T cells produce a protein named PD-1 that acts like an off switch for immune responses. This “checkpoint” helps keep T cells from improperly attacking healthy cells.

Source: https://news.wisc.edu/