'Drug factory' implants eliminate ovarian, colorectal cancer in mice
Immunotherapy treatment could begin human clinical trials this year

Date:
March 2, 2022
Source:
Rice University
Summary:
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.



FULL STORY ==========================================================================
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 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.



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"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 Jose'
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 ========================================================================== Story Source: Materials provided by Rice_University. Original written
by Jade Boyd. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Amanda M. Nash, Maria I. Jarvis, Samira Aghlara-Fotovat, Sudip
Mukherjee,
Andrea Hernandez, Andrew D. Hecht, Peter D. Rios, Sofia
Ghani, Ira Joshi, Douglas Isa, Yufei Cui, Shirin Nouraein,
Jared Z. Lee, Chunyu Xu, David Y. Zhang, Rahul A. Sheth, Weiyi
Peng, Jose Oberholzer, Oleg A. Igoshin, Amir A. Jazaeri, Omid
Veiseh. Clinically translatable cytokine delivery platform for
eradication of intraperitoneal tumors. Science Advances, 2022; 8
(9) DOI: 10.1126/sciadv.abm1032 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220302150351.htm

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