6/2/2021 New research optimizes body's own immune system to fight cancer -- ScienceDaily

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New research optimizes body's own immune system to fight

cancer
Date: May 14, 2021

Source: University of Minnesota

Summary: A new study shows how engineered immune cells used in new cancer therapies can overcome
physical barriers to allow a patient's own immune system to fight tumors. The research could im-
prove cancer therapies in the future for millions of people worldwide.

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FULL STORY

Lymphocytes illustration (stock image).

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A groundbreaking study led by engineering and medical researchers at the University

of Minnesota Twin Cities shows how engineered immune cells used in new cancer
therapies can overcome physical barriers to allow a patient's own immune system to
fight tumors. The research could improve cancer therapies in the future for millions of
people worldwide.

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6/2/2021 New research optimizes body's own immune system to fight cancer -- ScienceDaily

The research is published in Nature Communications, a peer-reviewed, open access, scientific journal pub-
lished by Nature Research.

Instead of using chemicals or radiation, immunotherapy is a type of cancer treatment that helps the patient's
immune system fight cancer. T cells are a type of white blood cell that are of key importance to the immune
system. Cytotoxic T cells are like soldiers who search out and destroy the targeted invader cells.

While there has been success in using immunotherapy for some types of cancer in the blood or blood-produ-
cing organs, a T cell's job is much more difficult in solid tumors.

"The tumor is sort of like an obstacle course, and the T cell has to run the gauntlet to reach the cancer cells,"
said Paolo Provenzano, the senior author of the study and a biomedical engineering associate professor in the
University of Minnesota College of Science and Engineering. "These T cells get into tumors, but they just can't
move around well, and they can't go where they need to go before they run out of gas and are exhausted."

In this first-of-its-kind study, the researchers are working to engineer the T cells and develop engineering
design criteria to mechanically optimize the cells or make them more "fit" to overcome the barriers. If these im-
mune cells can recognize and get to the cancer cells, then they can destroy the tumor.

In a fibrous mass of a tumor, the stiffness of the tumor causes immune cells to slow down about two-fold -- al-
most like they are running in quicksand.

"This study is our first publication where we have identified some structural and signaling elements where we
can tune these T cells to make them more effective cancer fighters," said Provenzano, a researcher in the Uni-
versity of Minnesota Masonic Cancer Center. "Every 'obstacle course' within a tumor is slightly different, but
there are some similarities. After engineering these immune cells, we found that they moved through the tumor
almost twice as fast no matter what obstacles were in their way."

To engineer cytotoxic T cells, the authors used advanced gene editing technologies (also called genome edit-
ing) to change the DNA of the T cells so they are better able to overcome the tumor's barriers. The ultimate
goal is to slow down the cancer cells and speed up the engineered immune cells. The researchers are working
to create cells that are good at overcoming different kinds of barriers. When these cells are mixed together, the
goal is for groups of immune cells to overcome all the different types of barriers to reach the cancer cells.

Provenzano said the next steps are to continue studying the mechanical properties of the cells to better under-
stand how the immune cells and cancer cells interact. The researchers are currently studying engineered im-
mune cells in rodents and in the future are planning clinical trials in humans.

While initial research has been focused on pancreatic cancer, Provenzano said the techniques they are devel-
oping could be used on many types of cancers.

"Using a cell engineering approach to fight cancer is a relatively new field," Provenzano said. "It allows for a
very personalized approach with applications for a wide array of cancers. We feel we are expanding a new line
of research to look at how our own bodies can fight cancer. This could have a big impact in the future."

In addition to Provenzano, the study's authors included current and former University of Minnesota Department
of Biomedical Engineering researchers Erdem D. Tabdanov (co-author), Nelson J. Rodríguez-Merced (co-au-
thor), Vikram V. Puram, Mackenzie K. Callaway, and Ethan A. Ensminger; University of Minnesota Masonic
Cancer Center and Medical School Department of Pediatrics researchers Emily J. Pomeroy, Kenta Yamamoto,
Walker S. Lahr, Beau R. Webber, Branden S. Moriarity; National Institute of Biomedical Imaging and Bioengin-
eering researcher Alexander X. Cartagena-Rivera; and National Heart, Lung, and Blood Institute researcher
Alexander S. Zhovmer, who is now at the Center for Biologic Evaluation and Research.

The research was funded primarily by the National Institutes of Health (NIH) and University of Minnesota Phys-
ical Sciences in Oncology Center, which receives funding from NIH's National Cancer Institute. Additional fund-
ing was provided by the American Cancer Society and the Randy Shaver Research and Community Fund. The

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University of Minnesota Imaging Center provided additional staff expertise. Some of the researchers also are
part of the University of Minnesota Center for Genome Engineering and the University's Institute for Engineer-
ing in Medicine.

Story Source:

Materials provided by University of Minnesota. Note: Content may be edited for style and length.

Journal Reference:

1. Erdem D. Tabdanov, Nelson J. Rodríguez-Merced, Alexander X. Cartagena-Rivera, Vikram V. Puram,

Mackenzie K. Callaway, Ethan A. Ensminger, Emily J. Pomeroy, Kenta Yamamoto, Walker S. Lahr, Beau
R. Webber, Branden S. Moriarity, Alexander S. Zhovmer, Paolo P. Provenzano. Engineering T cells to
enhance 3D migration through structurally and mechanically complex tumor microenvironments.
Nature Communications, 2021; 12 (1) DOI: 10.1038/s41467-021-22985-5

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University of Minnesota. "New research optimizes body's own immune system to fight cancer." ScienceDaily.
ScienceDaily, 14 May 2021. <www.sciencedaily.com/releases/2021/05/210514134222.htm>.

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