Chapter 1464: Chapter 1091: Freeing the Mind
The experintal pig had to undergo PET-CT scans and various blood tests, all of which were dynamically monitored at different intervals; nevertheless, each had to be checked periodically. Collecting experintal data is a tedious task, requiring researchers to endure and seek valuable clues within the dull numbers.
From the results of the subsequent checks, the experint didn’t look promising. NK cells still couldn’t overco the fatal weakness inherent in cell therapy – even after embedding the K factor, their nature as immunocytes remained unchanged, and they still couldn’t infiltrate solid tumors in large numbers.
Faced with these disheartening interdiate results, everyone gathered to discuss and learn from the experience, making adjustnts for the next experint. The correct path for the experint was slowly found through these modifications.
Far from being discouraged, everyone was filled with passion. This is the basic quality of a researcher. True scientific workers must be prepared to imrse themselves in the laboratory for decades or even a lifeti, sotis achieving nothing significant, or at best publishing a few aningless papers.
“Our NK cells are facing the sa limitations as CAR-T cells. Although they can express receptors for identifying specific tumor markers, which helps in treating blood cancers, they find it difficult to penetrate tumor tissues through the bloodstream. Furthermore, due to a lack of chemokine expression that aids in T cells infiltrating tumor tissues, and the presence of dense fibrotic matrix within solid tumors, their migration into and invasion of tumor cells is greatly hindered, which ans the therapeutic effect is bound to be limited,” began Tang Shun, leaning forward to kick off the discussion, admitting that this experint had seen no breakthroughs.
Lu Xiaolu held the experintal data in his hands, the papers wrinkled from being frequently reviewed: “Yes, it’s a challenge that we must overco to move forward. There are international thods involving direct local injection of CAR-T cells into tumors, but I feel this approach is pointless. Local cell injections may also reduce the risk of off-target effects. However, many solid tumors are tastatic, and local injections face the sa dilemma as surgical operations – they cannot completely and precisely eradicate the tumor. In other words, it’s not realistic to expect immune cells to act as a surgical knife – such an approach is destined to fail. There are also thods that use chemokines to diate the transport of CAR-T cells to enhance their targeting of tumors. For instance, the expression of CSF-1R in CAR-T cells triggers a response to CSF-1, which while enhancing signaling for cell proliferation, does not impact their cytotoxicity. However, in experints, even this approach has been rather arbitrary.”
Yang Ping thought he made a lot of sense, and pondering his own thoughts said, “The microenvironnt of solid tumors, while promoting tumor growth and proliferation, also suppresses the immune cells, including immunosuppressive cells like regulatory T cells, myeloid-derived suppressor cells, and tumor-related macrophages. Growth factors, local cytokines, and immunological checkpoint molecules like CTLA-4 and PD-1 in this composite environnt greatly limit the effectiveness of immune cells. Both genetically engineered T cells and NK cells face this issue. To address it, there are two approaches: either step outside the cellular frawork, using oncolytic viruses, or improve the immune cells so they can break through the blockade of the tumor microenvironnt. This brings us back to our starting point – the fatal flaws of both oncolytic viruses and immune cells.”
“In the United States, researchers have created Gr-1 antibodies through genetic engineering. These antibodies deplete myeloid-derived suppressor cells, thus enhancing the tumor-killing effect. Others have engineered enzys that degrade ECM, which can dissolve barriers and help immune cells break through the physical constraints within solid tumors. But these technologies have been around for years, and I haven’t seen any substantive breakthroughs,” said Li Yingtong, who had worked at the Whitehead Laboratory at the Massachusetts Institute of Technology and was very knowledgeable about these cutting-edge Arican technologies.
It certainly is a challenge; if it weren’t, there would be no need for so many laboratories and top talents working together to solve it, nor would Yang Ping have spent so much money. He never thought of solving this issue easily; that would be unrealistic.
The first experint didn’t produce promising results, but it was just the beginning. Through this experint, the team mastered the complete set of NK cell therapy techniques and knew how to improve them subsequently. Everyone didn’t have high expectations for the first trial; it was expected to be rough, flawed, even entirely wrong at tis, but this never deterred everyone from continuing their exploration.
“Actually, we should be more open-minded and not confine ourselves within the limits of the existing technologies. If we restrict ourselves to what’s considered cutting-edge in Europe and Arica, it will be very difficult for us to make a breakthrough. If NK cells don’t work, we can use macrophages; they have good penetration. If that doesn’t work, we can use them for cell recombination, creating a new type of cell. Rember, we are now truly entering an uncharted territory, with no references, so all our problems depend on our own thods,” said Yang Ping after listening to their discussion. It was clear that everyone was still constrained by Western cutting-edge technology.
“Macrophages?” Tang Shun asked, as there was very little research in this area.
Yang Ping nodded: “Yes, macrophages have their inherent disadvantages, but we can genetically recombine them with NK cells.”
Professor Yang’s ideas are always so imaginative, always capable of leaping out of habitual thinking. Tang Shun, Lu Xiaolu, and Li Yingtong pondered for a long ti and indeed, found the idea quite novel.
“Shall we proceed along this train of thought next?” Tang Shun could no longer grasp the strategic direction of the experint.
Yang Ping confidently stated: “Try more and do not fear failure. We are essentially blazing a trail in a wasteland; we must step forward and then change course if necessary. We learn advanced techniques from Europe and Arica to surpass them, not to remain in perpetual admiration and follow. Therefore, we must have confidence. At this stage, we are at the forefront, and we can only rely on ourselves to solve all problems.”
Yang Ping’s words liberated everyone’s minds from constraints, breaking away from the intangible authority of Europe and Arica and establishing strong self-confidence, an indispensable elent in independent scientific research.
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Lin Lan of Nandu dical University’s genetics laboratory is also now swamped. She needs to conduct genetic sequencing on immunocytes and related cytokines, and to complete the sequencing work, Lin Lan must utilize single-cell sequencing technology.
Single-cell sequencing, a breakthrough biotechnology, has been gaining favor in the dical field in recent years. With this technology, researchers can conduct life science research on the single-cell level, performing high-throughput sequencing analysis of genos, transcriptos, and epigenos, and categorizing and annotating cell populations based on cellular characteristics to create a cell atlas.
The Human Cell Atlas project, launched in 2016 by Aviv, Sarah, and others, is a major international collaborative project on a par with the “Human Geno Project.” The goal is to classify and define all human cell types based on unique molecular-level information, interrelate this information with traditional cellular characterization, and identify unique gene expression patterns, physiological states, developntal trajectories, and location information in each and every cell type within an individual. This will provide deeper and more complex cellular genetic level information for the overall health of humanity.
For Lin Lan, this task is not difficult, especially as it is in her area of expertise. With the support of Digital Human Technology, Lin Lan’s genetic sequencing work is much simplified, because Professor He, in the process of creating a Digital Human, has already accumulated a wealth of data on cells in this regard. With these data, he was able to construct digital cells and then use them to build a digital human body, pushing Digital Human to the level of a Functional Digital Human. Lin Lan can utilize these readily available data, reducing the amount of work she needs to do by almost half.
Furthermore, with the close cooperation established between Nandu dical University and the supercomputing center of Nandu Province, Lin Lan’s sequencing work is going very smoothly with the help of the supercomputer. Her first comparative sequencing experint shows: indeed, there is an overlap between the K factor and various immune cell gene segnts. This result is greatly encouraging to everyone; it seems that Professor Yang’s hypothesis might be correct. Of course, whether it is truly correct still requires the completion of all sequencing and comparison work.
Professor Zhang Zhiwei from the virology departnt at Nandu dical University is also in a not-so-optimistic situation, as he has now reached a wilderness area with no references, completely dependent on forging ahead on his own.
All existing viral vectors, no matter how advanced, are hard to escape from being attacked by the immune system. How to select a safe virus carrier that can both infect all cell types and evade the immune system is an extrely difficult task.
Moreover, it’s necessary to recompose this viral vector anew, integrating so functional segnts of immunocytes—how to recompose and how to control the characteristics of the virus post-recombination are both challenges.
Professor Zhang has scoured related papers worldwide, and no one has reached this step, not even the most advanced research teams which are still focused on the treatnt approach using oncolytic viruses. Now their topic is entirely different from oncolytic virus therapy.
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