22 maart 2023: Bron: SCIENCE ADVANCES 2 Mar 2022 Vol 8Issue 9

Met dank aan Jacques die me op deze behandeling wees. Ik heb er verder nog wat meer informatie bij gezocht. 

Bio-ingenieurs van Rice University en onderzoekers van University of Texas MD Anderson Cancer CenterUniversity of Virginia en University of Houston (Amerika) hebben aangetoond dat ze eierstokkanker en darmkanker  in een vergevorderd stadium bij muizen in slechts zes dagen kunnen elimineren en de muizen genezen met een behandeling met Interleukine-2 (IL-2) via speciale ‘geneesmiddelenfabriekjes', bolletjes (beads) ingebracht waarmee continu hoge doses van Interleukine-2 (IL-2) kunnen worden toegediend. Waarmee de ernstige bijwerkingen die IL-2 op kan roepen grotendeels vermeden werd. 

Deze aanpak zou ook bij andere vormen van kanker met solide tumoren, zoals bij alvleesklierkanker, leverkanker, asbestkanker - mesothelioma enz. kunnen worden toegepast schrijven de onderzoekers. 

Inmiddels is in Amerika een patiëntenstudie gestart bij patiënten met eierstokkanker, zie dit studieprotocol 

Uit Medzine die een vertaling maakte van een Engelstalig artikel een citaat:

Bolletjes die IL-2 produceren

In het huidige onderzoek gebruikten de onderzoekers speciale ‘geneesmiddelenfabriekjes', bolletjes (beads) waarmee continu hoge dosissen van IL-2 kunnen worden toegediend. Er werd gekeken naar de effectiviteit en of systemische bijwerkingen van cytokines konden worden vermeden. Het idee was dat de bolletjes een sterkere immuunrespons uitlokken dan bestaande IL-2 behandelingsregimes omdat de beads hogere concentraties van het eiwit rechtstreeks aan tumoren afgeven.

De medicijnproducerende bolletjes kunnen met een minimaal invasieve operatie worden geïmplanteerd. Elk bolletje bevat cellen die zijn gemanipuleerd om IL-2 te produceren en is ingekapseld in een beschermend omhulsel. Er werden alleen componenten gekozen die eerder veilig waren gebleken voor gebruik bij mensen, en de veiligheid van deze nieuwe behandeling werd in meerdere testen aangetoond.

Deze week worden presentaties gegeven over deze vorm van immuuntherapie. Zie daarvoor dit schema:
Published: Mar. 22, 2023 at 8:00 AM EDT|Updated: 8 hours ago

NATICK and QUINCY, Mass., March 22, 2023 /PRNewswire/ -- Avenge Bio, Inc. ("Avenge" or the "Company"), a biotechnology company developing the LOCOcyte™ Immunotherapy platform for the precision administration of potent immune effector molecules to treat solid tumors, today announced their posters were selected for presentation at the Society of Gynecologic Oncology's (SGO) 2023 Annual Meeting on Women's Cancer in Tampa, Florida on March 25-28, 2023 and the American Association for Cancer Research (AACR) Annual Meeting 2023 in Orlando, Florida on April 14-19, 2023.

AVB-001, developed in the LOCOcyte™ platform, consists of proprietary engineered allogeneic human cells. The cells are encapsulated in a pro-inflammatory biomaterial that are delivered to the local tumor environment and generate high, sustained concentrations of human IL-2. The product initiates a robust and durable, local and systemic immune response while avoiding toxicities associated with systemic immunotherapies.

Avenge's most advanced product candidate, AVB-001, produces native IL-2 immunotherapy and is initially being studied in metastatic peritoneal cancers such as ovarian cancer. Avenge has additional pipeline candidates for the treatment of a wide range of cancers including pancreatic, lung and breast cancers.

Presentation Details:

Conference: Society of Gynecologic Oncology's (SGO) 2023 Annual Meeting on Women's Cancer
Location: Tampa Convention Center | Tampa, FL | Exhibit Hall
Session Title: Poster Session 1
Poster Number: 1271
Poster Title: Favorable preclinical efficacy and safety profile of AVB-001, a novel IL-2 cell-based immunotherapy that eradicates ovarian cancer in mouse tumor models and supports first-in-human clinical development
Author: Guillaume Carmona, PhD (Avenge Bio, Inc.)
Date: Sunday, March 26, 2023
Time: 2:00-3:00 PM ET

Conference: American Association for Cancer Research (AACR) Annual Meeting 2023
Location: Orange County Convention Center | Orlando, FL | Room W414
Session Type: Methods Workshop (WM007) – Emerging Platforms for Cancer Immunotherapy
Session Title: Developing clinically translatable cytokine factories for cancer immunotherapy
Session Chair & Presenter: Omid Veiseh, PhD (Rice University)
Date: Saturday, April 15, 2023
Time: 12:30-1:00 PM ET

Conference: American Association for Cancer Research (AACR) Annual Meeting 2023
Location: Orange County Convention Center | Orlando, FL | Poster Section 46
Session Title: Phase I Clinical Trials in Progress
Poster Number: 10
Abstract Presentation Number: CT122
Poster Title: A phase 1/2 open-label, multicenter, dose escalation and expansion study of AVB-001, an intraperitoneally administered, cell-generated, human IL-2 immunotherapy in patients with platinum-resistant, high-grade, serous adenocarcinoma of the ovary, primary peritoneum, or fallopian tube
Author: Shannon N. Westin, MD, MPH (MD Anderson Cancer Center)
Date: Monday, April 17, 2023
Time: 1:30-5:30 PM ET

Conference: American Association for Cancer Research (AACR) Annual Meeting 2023
Location: Orange County Convention Center | Orlando, FL | Poster Section 35
Session Title: Late-Breaking Research: Immunology I
Poster Number: 17
Abstract Presentation Number: LB101
Poster Title: Cell-generated IL12 combined with PD-1 inhibition produces local and abscopal immune activation to eradicate metastatic melanoma and pancreatic cancer
Author: Amanda Nash, BS (Rice University)
Date: Monday, April 17, 2023
Time: 9:00 AM-12:30 PM ET

The posters will be available on the Presentations and Publications section of www.avengebio.com following the conference.

About LOCOcyte™ Platform

Our LOCOcyteTM allogeneic cell-based immunotherapy platform enables potent localized modulation of the immune system which also precipitates a systemic immune response, allowing us to treat previously intractable cancers. The technology leverage three unique advantages:

  1. Potent immune effector molecules are generated by synthetically engineering allogeneic cells creating a ready-to-use therapy,
  2. Therapy is localized in proximity to the primary tumor site and generates innate and adaptive immune response, and
  3. The immunomodulator trains the patient's immune system generating a robust immune response that seeks and eradicates distal metastasis without systemic toxicity.

About Avenge Bio

Avenge Bio, Inc. ("Avenge") is an oncology-focused biotechnology company developing transformative cell-based immunotherapeutic products for the treatment of intractable solid tumors by incorporating its LOCOcyte™ platform. The LOCOcyte™ platform leverages proprietary engineered cells delivered to the local tumor environment that generate high concentrations of immune effector molecules in proximity to the tumor. This initiates a robust, local, and durable systemic immune response while avoiding toxicities associated with systemic immunotherapies. Avenge's most advanced product candidate, AVB-001, produces native IL-2 immunotherapy and is initially being studied in metastatic peritoneal cancers such as ovarian cancer. Avenge has additional pipeline candidates for the treatment of a wide range of cancers including pancreatic, lung and breast cancers. Avenge was founded in 2019 based upon technology developed in the laboratory of Omid Veiseh, Ph.D. and has an exclusive license from Rice University for this technology. To learn more about Avenge visit: www.avengebio.com and follow us on LinkedIn and Twitter.

View original content to download multimedia:

SOURCE Avenge Bio, Inc.

The above press release was provided courtesy of PRNewswire. The views, opinions and statements in the press release are not endorsed by Gray Media Group nor do they necessarily state or reflect those of Gray Media Group, Inc.

De vertaling van Medzine is gemaakt vanuit dit artikel met daarin via een video een verdere uitleg: 'Drug factory' implants eliminate ovarian, colorectal cancer in mice.  

The researchers used implantable "drug 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 Veiseh, Amanda 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.

"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."

Interleukin-2 is a cytokine, a protein the immune system uses to recognize and fight disease. It is an FDA-approved cancer treatment, but Nash, a graduate student in Veiseh's group and the study's lead author, said the drug factories provoke a stronger immune response than existing interleukin-2 treatment regimens because the beads deliver higher concentrations of the protein directly to tumors.

"If you gave the same concentration of the protein through an IV pump, it would be extremely toxic," Nash said. "With the drug factories, the concentration we see elsewhere in the body, away from the tumor site, is actually lower than what patients have to tolerate with IV treatments. The high concentration is only at the tumor site."

Nash said the same general approach used in the study could be applied to treat cancers of the pancreas, liver, lungs and other organs. The drug factories could be placed next to tumors and within the linings that surround those organs and most others, she said. And if a different cytokine is needed to target a specific form of cancer, the beads can be loaded with engineered cells that make that immunotherapeutic compound.

The bead's outer shell shields its cytokine-producing cells from immune attacks. The shells are made of materials the immune system recognizes as foreign objects but not as immediate threats, and Veiseh's lab leveraged that in its design.

"We found foreign body reactions safely and robustly turned off the flow of cytokine from the capsules within 30 days," he said. "We also showed we could safely administer a second course of treatment should it become necessary in the clinic."

Avenge Bio, a Massachusetts-based startup co-founded by Veiseh, has licensed the cytokine-factory technology from Rice.

Additional co-authors include Maria Jarvis, Samira Aghlara-Fotovat, Sudip Mukherjee, Andrea Hernandez, Andrew Hecht, Yufei Cui, Shirin Nouraein, Jared Lee, David Zhang and Oleg Igoshin of Rice; Peter Rios, Sofia Ghani, Ira Joshi and Douglas Isa of CellTrans Inc.; Chunyu Xu and Weiyi Peng of the University of Houston; Rahul Sheth of MD Anderson; and José Oberholzer of both CellTrans Inc. and the University of Virginia.

The research was funded by the Cancer Prevention Research Institute of Texas (RR160047), Avenge Bio, the Emerson Collective, the Welch Foundation, the Rice University Academy of Fellows, the National Science Foundation (1842494) and the National Institutes of Health (R01DK120459).

Jazaeri receives compensation as a consultant on Avenge Bio's scientific advisory board and has disclosed the relationship to MD Anderson in accordance with its conflict-of-interest policy. Nash, Jarvis, Aghlara-Fotovat, Mukherjee, Hecht, Igoshin, Zhang and Veiseh declared interests via patents filed by Rice on the cytokine factories. Igoshin, Veiseh and Oberholzer are paid consultants for Avenge Bio. Nash, Zhang, Sheth, Oberholzer, Jazaeri and Veiseh hold equity in Avenge Bio.

Video: https://youtu.be/8HegA8q807o



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