Nature sub-journal: Step on the accelerator for the immune system, MIT develops IL-12+ alum therapy, which effectively kills tumors and has fewer side effects

Written | Edited by nagashi | Typography by Wang Duoyu | Shui Wenwen cancer, known as the "King of Diseases" because of its intractability and complexity
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Fighting cancer is like life and death on a racing track - killing cancer cells faster than they multiply
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On this life-and-death track, human beings have always had a top racing car-the immune system
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Attacking tumors by stimulating the immune system is a promising cancer treatment
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Today, scientists are working on two complementary strategies to achieve this goal: "turning off the brakes"—unblocking the immune system from tumors; and "stepping on the gas"—activating the immune system with immunostimulatory drugs
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The former has already launched immune checkpoint inhibitor drugs including anti-PD-1/PD-L1 monoclonal antibodies, while the latter has no successful precedent
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On January 10, 2022, a research team from the Massachusetts Institute of Technology (MIT) published a research paper entitled: Intratumourally injected alum-tethered cytokines elicit potent and safer local and systemic anticancer immunity in Nature Biomedical Engineering, a sub-journal of Nature
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The study developed a new method to prime the immune system by combining the cytokine IL-12 with aluminum hydroxide (alum) and delivering it to tumors, activating tumor immunity while avoiding the use of immune-stimulating drugs throughout the body possible toxic reactions
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In a study in mice, the research team used this therapeutic strategy with an anti-PD-1 mAb to successfully activate the immune system and eliminate multiple types of tumors
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"IL-12 is just the beginning, and this treatment strategy may be applicable to any other immune-stimulating drug , "
said the study's corresponding author, Professor Darrell Irvine, associate director of the Koch Institute for Integrative Cancer Research at MIT .
The treatment technology has been patented and licensed to a start-up company, which is expected to begin clinical trials by the end of 2022 .
Bioworld: We speculate that Strand Therapeutics may have licensed the technology, but it hasn't been announced, so we can't be sure .
Step on the gas as tumors develop, they secrete molecules that disable nearby T cells and other immune cells, allowing the tumor to grow uncontrollably .
It's as if cancer cells put the "brake" on the immune system .
Immune checkpoint inhibitors can be used to activate the immune system, but only for certain types of cancer, many others are resistant to this treatment .
Combining immune checkpoint inhibitors with drugs that stimulate the immune system may make cancer immunotherapy effective for more patients .
Cytokines are immune chemicals naturally produced by the body that activate the body's immune system .
In clinical trials, however, these drugs have shown too many toxic side effects, such as flu-like symptoms and even organ failure .


















Professor Dane Wittrup, one of the corresponding authors of the study, said: "If a patient is exposed to a large number of cytokines, their whole body will react, which will have very strong toxic side effects, so it is difficult to achieve the desired anti-tumor effect
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" To avoid these side effects, the research team has been investigating ways to deliver cytokines in a more targeted manner
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In June 2019, the team published a paper in Science Translational Medicine in which they attached the cytokines IL-12 and IL-2 to collagen-binding proteins that bind to collagen that is abundantly expressed in tumors, thereby binding these cells to Factors are specifically delivered to tumor tissue
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This therapeutic strategy worked well in mouse studies, but they hoped to find a way to make the cytokine bind more strongly to the tumor
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Now, in their latest study, they replaced the collagen-binding protein with aluminum hydroxide
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Aluminum hydroxide, also known as alum, is often used as a vaccine adjuvant (a drug that helps boost the immune response) and is also a food additive, such as when fried dough sticks are added as a bulking agent, but because alum contains aluminum Excessive intake of ions will affect the body's absorption of iron, calcium and other ingredients, resulting in osteoporosis, anemia, and even affect the development of nerve cells
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Therefore, some nutrition experts propose to try to eat less food containing alum
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However, it is such a notorious food additive that has become the key to the success of this latest study! Dr Yash Agarwal, lead author of the study, said: "A major advantage of alum is that the particles are micron-sized, so when you inject them into a human or mouse, they stay where you inject them for weeks.
, sometimes even for months
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"Stronger tumor suppression, fewer toxic side effects To test the effectiveness of this treatment, the researchers injected mice with either IL-12 or IL-2 bound to alum particles and injected the mice every few days.
Immune checkpoint inhibitor with anti-PD-1 mAb
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In three mouse models of cancer, researchers found that tumors were eliminated in 50 to 90 percent of the mice
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In a mouse model of breast cancer lung metastases A single injection at the breast cancer site also cleared the metastatic tumor
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In addition, the IL-12-alum particles showed the ability to stimulate the immune system to fight the tumor even without the combination of anti-PD-1 mAb
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IL-12- Alum particles promote systemic immunity in an orthotopic 4T1 breast cancer model Further studies have shown that IL-12 stimulates the production of another cytokine called interferon gamma, and these two molecules work together to activate T cells, dendritic cells and macrophages
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Not only that, but this therapy stimulated memory T cells to respond to tumor regeneration
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What's more, mice treated with IL-12-alum particles did not develop any systemic injections of IL Side effects
at
-12.
IL-12-alum particles remain in tumor tissue and produce negligible systemic toxicity after administration The startup that licensed the technology plans to test IL-12 on its own for the first time by the end of this year -Alum particles, if the therapy proves to be safe, they hope to further test the effect of IL-12-Alum particles in combination with immune checkpoint inhibitors
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All in all, this research develops a method that activates the immune system with minimal side effects The immunotherapeutic strategy-combining alum particles with the cytokine IL-12 and then delivering them directly into the tumor tissue, IL-12-alum particles will stay at the tumor site for several weeks, reducing toxic side effects and stimulating the production of interferon-γ.
Generate and activate the immune system to initiate tumor immune responses
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IL-12-alum particles activate the immune system.
The combination of IL-12-alum particles and the immune checkpoint inhibitor anti-PD-1 monoclonal antibody has shown good therapeutic effects in a variety of mouse cancer models and can treat metastatic disease tumor
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Professor Darrell Irvine said: "This new method of attaching molecules to alum could also be used to deliver other types of immunostimulatory drugs
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This type of drug
involving 'tapping the gas' is largely unprecedented and we hope this will provide Testing these drugs opens the way" References: https:// .
edu/2022/method-delivering-immune-stimulating-drugs-cancer-immunotherapy-0110 is open for reprinting.
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