Scientists at UC San Francisco developed a method to precisely reprogram these cancer-fighting cells directly inside the body, potentially eliminating those barriers.
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In a major breakthrough, scientists at UC San Francisco developed a method to precisely reprogram these cancer-fighting cells directly inside the body, potentially eliminating those barriers. It is the first time that scientists have integrated a large sequence of DNA at a specific site in human T cells without removing them from the body.
For many years, one of the most effective tools against some blood cancers, called CAR-T therapy, required an extensive procedure. Doctors extract the patient’s immune cells, ship them to a specialized facility where they are genetically reprogrammed to fight the deadly disease, then ship them back for infusion into the patient’s bloodstream. It revolutionized cancer treatment but the time and expense place it out of reach for several patients.
In a major breakthrough, scientists at UC San Francisco developed a method to precisely reprogram these cancer-fighting cells directly inside the body, potentially eliminating those barriers. It is the first time that scientists have integrated a large sequence of DNA at a specific site in human T cells without removing them from the body. This targeted approach, which did better than the standard method, is a breakthrough that goes beyond CAR T to advance the fields of cell and gene therapy overall, according to a report featured in University of California. 1
In experiments using mice with humanized immune systems, described March 18 in Nature, the researchers used the method to successfully cure aggressive leukemia, multiple myeloma, and even a solid tumor. Scientists believe the latest method will lead to an off-the-shelf therapy, like a vaccine, that could one day be given to anyone with the same condition.
“I think this is just the beginning of a big wave of new therapies that will be truly transformational and save a lot of lives,” said Justin Eyquem, Ph.D., an associate professor of medicine at UCSF, member of the Weill Cancer Hub West, and the senior author of the new paper. “I’m incredibly excited to be part of it.”
CAR-T cell therapy works by giving T cells — the immune system’s disease fighters — new genetic instructions to recognize and destroy cancer cells. These instructions come in the form of chimeric antigen receptors (CARs), which are molecules that protrude from the surface of T cells like antennae. When a CAR binds to specific proteins on a cancer cell’s surface, it triggers the T cell to attack and kill the tumor cell.
Seven CAR-T cell therapies are currently approved for use in blood cancers by the U.S. Food and Drug Administration. But these are bespoke treatments that are individually tailored to each patient and must be manufactured in specialized facilities. The process takes weeks and costs $400,000 to $500,000. Patients also must undergo chemotherapy to clear space in their bone marrow for the new T cells — a punishing process that some cannot tolerate, added the University of California report.
“It’s become a global access issue,” Eyquem said. “There has been a big push in the field to try to move to directly producing these cells in the body.” Working with scientists at the Gladstone Institutes, Duke University, and Innovative Genomics Institute, Eyquem designed a two-particle system. One of the particles carried CRISPR-Cas9 gene-editing machinery — the molecular scissors required to alter genes — directly to T cells circulating in the body.
Because it uses the CRISPR-Cas9, the method makes edits at a predetermined place in the genome — a big advantage over the current method of randomly integrating CAR genes that can in rare cases result in secondary cancers.
The second particle carried the new DNA for the cancer-fighting CAR. It would only insert at a specific location in the T cell genome with a molecular “on switch” that is only activated in T cells. The particles also were engineered to find T cells and evade immediate destruction by the immune system.
“When you manufacture these cells outside the body, you can do a lot of quality control to make sure you only end up with re-engineered T cells,” said Eyquem. “We can’t do that inside the body, so we really needed to optimize the approach upfront to avoid genetically altering any other cells.”
Recently, Dr. Saurabh Sethi, AIIMS-trained gastroenterologist and liver specialist, also educated at Harvard and Stanford, took to his Instagram account and listed foods that can reduce the risk of cancer. In a post shared on Instagram, the gut doctor said, “Cancer rates are rising - especially in younger adults. Here are 5 foods linked to lower cancer risk I encourage patients to eat regularly.” 2
1. Purple Sweet Potato: The vegetable can prevent the risk of cancer. Presence of antioxidants can help you fight cancer that may include colon and breast cancer. Extracts from the vegetable can inhibit the growth of several cancer cells. According to Dr Sethi, “Rich in anthocyanins – antioxidants linked to reduced inflammation and cellular damage. Lab studies show they may slow colon cancer growth. More color=more protective compounds.”
2. Broccoli Sprouts & Microgreens: Broccoli sprouts contain high amounts of carotenoids and antioxidant properties. They can prevent degenerative conditions like cardiovascular diseases, diabetes, skin damage, and cancers such as prostrate cancer and breast cancer. Dr Sethi said, “They are loaded with sulforaphane - a compound that activates detox and antioxidant pathways. Contain 20-100x more precursors than mature broccoli. Small serving. Poweful chemistry.”
3. Kiwis: Kiwi fruit are exceptionally high in vitamin C and contain an array of other nutrients, notably nutritionally relevant levels of dietary fibre, potassium, vitamin E and folate, as well as various bioactive components, including a wide range of antioxidants, phytonutrients and enzymes, that act to provide functional and metabolic benefits. The fruit provides beneficial compounds that offer anti-cancer effects.
“high in vitamin C, fibre, and polyphenols. Studies show improved DNA protection and antioxidant status with regular intake. Also supports digestion and bowel regularity,” added Dr Sethi.
4. Green Tea: Green tea is one of most widely consumed drinks all over the world. Unlike the conventional tea, it is marginally processed that helps in preserving the antioxidants in particular catechins, the main compounds behind its myriad advantages. Whether you sip green tea to promote weight loss, improve digestion, or glowing skin, it provides vast benefits that can support both physical and overall well-being. Dr Sethi said green tea is “rich in EGCG – studied for supporting tumor-suppressor pathways. Population studies link regular intake with lower cancer risk. Matcha=higher concentration.”
5. Beans: The AIIMS-trained doctor recommended beans as part of healthy diet to reduce cancer risks. It is a rich source of protein and packed with essential fibre that can offer an array of health benefits. He said consumption of half cup of beans offer 7 to 8 grams of fibre. Most adults need 25 to 38 grams per day but fall short. “Higher fibre intake is linked to lower colorectal cancer risk. Feed your microbiome. Protect your colon,” emphasised Dr Sethi.
FAQs
How does the new in-body CAR-T therapy differ from traditional CAR-T treatments?
Traditional CAR-T therapy involves extracting T cells from the patient, modifying them externally, then reinfusing them, which is time-consuming and costly. The new in-body CAR-T method developed by UCSF uses CRISPR-Cas9 to edit T cells directly inside the body, eliminating the need for cell extraction and external modification, potentially reducing treatment time and cost.
What are the cost advantages of the in-body CAR-T therapy compared to current treatments?
Current FDA-approved CAR-T therapies cost between $400,000 and $500,000 due to complex manufacturing and chemotherapy requirements. The in-body CAR-T approach aims to simplify production by reprogramming T cells inside the body, which could lower costs significantly and improve accessibility by bypassing external manufacturing facilities and extensive preparation.
Can the in-body CAR-T therapy be used for solid tumors as well as blood cancers?
Yes, experiments in mice with humanized immune systems demonstrated that the in-body CAR-T therapy successfully treated aggressive leukemia, multiple myeloma, and even solid tumors, suggesting its potential applicability beyond blood cancers.
What dietary choices are recommended to help reduce the risk of cancer?
A healthy diet rich in fruits, vegetables, proteins, and whole grains can help lower cancer risk. Specifically, foods like purple sweet potatoes, broccoli sprouts, kiwis, green tea, and beans, which are high in antioxidants, fiber, and bioactive compounds, have been recommended by experts like Dr. Saurabh Sethi for their cancer risk-reducing properties.
How does CRISPR-Cas9 improve the safety of in-body CAR-T cell editing?
CRISPR-Cas9 enables precise gene editing at predetermined genome locations, reducing the risk of random gene integration that can sometimes lead to secondary cancers in traditional CAR-T therapy. This targeted editing enhances safety by minimizing unintended genetic alterations.
University of California|Scientists create cancer-fighting immune cells right in the body
AIIMS-trained gastroenterologist Dr. Saurabh Sethi via Instagram| 5 Foods Linked To Lower Cancer
Disclaimer: This content is for general informational purposes only and should not replace professional medical advice. Always consult a qualified healthcare provider with any questions about your health or treatment options.
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