For the first time, researchers at the University of British Columbia have\u00a0demonstrated\u00a0how to reliably produce an important type of human immune cell-known as\u00a0helper T cells-from stem cells\u00a0in a controlled laboratory setting.\u00a0<\/p>\n
The findings, published today in\u00a0Cell Stem Cell, overcome a major hurdle that has limited the\u00a0development,\u00a0affordability\u00a0and large-scale manufacturing\u00a0of cell therapies. The discovery could pave the way for more accessible\u00a0and effective\u00a0off-the-shelf treatments for\u00a0a wide range of\u00a0conditions\u00a0like cancer, infectious diseases, autoimmune disorders and more.\u00a0<\/p>\n
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Engineered cell therapies are transforming modern medicine, This study addresses one of the biggest\u00a0challenges\u00a0in\u00a0making these\u00a0lifesaving\u00a0treatments accessible to more people,\u00a0showing\u00a0for the first time a reliable and scalable way to grow multiple immune cell types.”\u00a0<\/p>\n
\n <\/p>\nDr. Peter Zandstra,\u00a0co-senior author, professor\u00a0and director of the UBC School of Biomedical Engineering<\/p>\n
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The promise\u00a0and challenge\u00a0of living drugs\u00a0<\/p>\n
In recent years, engineered cell therapies, such as CAR-T treatments for cancer, have delivered dramatic and lifesaving results for patients with otherwise untreatable disease. These therapies work by reprogramming human immune cells to recognize and attack illness,\u00a0essentially turning\u00a0the cells into\u00a0‘living\u00a0drugs’.\u00a0<\/p>\n
Despite their\u00a0tremendous\u00a0promise, cell therapies\u00a0remain\u00a0expensive, complex to produce and inaccessible to many patients worldwide. One major reason is that most current treatments are made from a patient’s own immune cells, requiring weeks of customized manufacturing\u00a0for each\u00a0patient.\u00a0<\/p>\n
“The\u00a0long-term\u00a0goal is to\u00a0have off-the-shelf cell therapies that are\u00a0manufactured\u00a0ahead of time\u00a0and on a larger scale\u00a0from a\u00a0renewable source like stem cells,” said\u00a0co-senior author Dr. Megan Levings, a professor of surgery and biomedical engineering at UBC.\u00a0“This\u00a0would make\u00a0treatments much\u00a0more cost-effective\u00a0and ready when patients need\u00a0them.”\u00a0<\/p>\n
Cell therapies\u00a0for cancer\u00a0work\u00a0best\u00a0when\u00a0two\u00a0types\u00a0of immune cell\u00a0are present:\u00a0killer T cells<\/a>, which\u00a0directly attack infected or cancerous cells, and helper T cells,\u00a0which\u00a0act as the immune system’s conductors-detecting\u00a0health threats, activating other immune cells and sustaining\u00a0the\u00a0immune responses over time.\u00a0<\/p>\n
Although\u00a0progress has been made\u00a0using stem cells to\u00a0generate\u00a0killer T cells\u00a0in the lab, scientists have so far been unable to reliably produce helper T cells.\u00a0<\/p>\n
“Helper T cells are essential for a strong and lasting immune response,”\u00a0said\u00a0Dr. Levings.\u00a0“It’s critical that we have both to maximize the efficacy\u00a0and flexibility\u00a0of off-the-shelf therapies.”\u00a0<\/p>\n
A\u00a0big step toward\u00a0stem cell-grown therapies\u00a0<\/p>\n
In the new study, the\u00a0UBC researchers\u00a0were able to\u00a0solve\u00a0this long-standing challenge-adjusting key biological signals during\u00a0cell\u00a0development\u00a0to\u00a0precisely\u00a0control whether stem cells\u00a0developed into either\u00a0helper or killer T cells.\u00a0<\/p>\n
The team discovered that a developmental signal called\u00a0Notch\u00a0plays a critical but time-sensitive role. While Notch is needed early in immune cell development, if the signal\u00a0remains\u00a0active for too long, it prevents helper T cells from forming.\u00a0<\/p>\n
“By precisely tuning when\u00a0and how much\u00a0this signal is reduced, we\u00a0were able to direct stem cells to become either helper or killer T cells,”\u00a0said\u00a0co-first author Dr. Ross Jones,\u00a0a\u00a0research\u00a0associate\u00a0in the Zandstra Lab. “We\u00a0were able to do\u00a0this in\u00a0controlled laboratory conditions\u00a0that\u00a0are\u00a0directly applicable in\u00a0real-world\u00a0biomanufacturing, which is\u00a0an essential step toward turning\u00a0this\u00a0discovery into a viable therapy.”\u00a0<\/p>\n
Importantly, the\u00a0researchers\u00a0demonstrated\u00a0that the\u00a0lab-grown\u00a0helper T cells\u00a0didn’t\u00a0just resemble\u00a0real immune\u00a0cells-they behaved like them.\u00a0The cells showed markers of healthy\u00a0mature\u00a0cells, carried a diverse range of immune\u00a0receptors\u00a0and could specialize into subtypes\u00a0that\u00a0play distinct roles in immunity.\u00a0<\/p>\n
“These cells look and act like genuine human helper T cells,”\u00a0said\u00a0co-first author Kevin Salim,\u00a0a UBC PhD student in the Levings Lab. “That’s critical for future therapeutic\u00a0potential.”\u00a0<\/p>\n
The researchers say the\u00a0ability to generate both helper and killer T cells-and to control the balance between them-will\u00a0significantly improve\u00a0the efficacy of<\/a> stem cell-grown immune therapies in the future.\u00a0<\/p>\n
“This is a major step forward in our ability to develop scalable and affordable immune cell therapies,” said Dr. Zandstra.\u00a0“This\u00a0technology\u00a0now forms the\u00a0foundation\u00a0for\u00a0testing the role of helper T cells\u00a0in\u00a0supporting\u00a0the elimination of cancer cells\u00a0and\u00a0generating\u00a0new types of helper T cell-derived cells,\u00a0such as regulatory T cells,\u00a0for clinical applications.”\u00a0<\/p>\n
Source:<\/p>\n
University of British Columbia<\/a><\/p>\n
Journal reference:<\/p>\n