"Oh, Lady Windsor..."
"No need to say more, this is just our private conversation, you know I’m telling the truth, but can’t admit it; are we really already faltering?"
...
At night, the Nandu Sanbo Research Institute was brightly lit.
Yang Ping did not participate in any discussions about Wu Changde’s press conference; he didn’t even have ti to watch the news. He and Academician Chen Yongnian’s team were conducting a cross-temporal joint research effort.
The video conferencing system connected Nandu and Beijing. On Academician Chen’s side, the laboratory showed seven or eight screens displaying gene maps and affinity simulation data of different serotypes of adenovirus vectors. On Yang Ping’s side, the large screen displayed Shen Guohua’s real-ti updated tumor single-cell sequencing results and immune state analysis.
Yang Ping was well aware that although this exploration was a stopgap asure, his intuition told him that he could find a stable target for pancreatic cancer that complented the K Factor, and might even find another K Factor.
"The purplish-blue cell group has a very consistent upregulation of receptor B and can serve as a second target." Academician Chen pointed at the data. "Our stock of 35-type vectors has a natural fibrin with moderate affinity to receptor B, which can be increased by more than fifty tis through genetic modification while maintaining the basic recognition capability for receptor A."
"But the logical circuit for dual-target validation must be foolproof." Yang Ping stared at the gene circuit design, "The AND gate design must be precise, only when both A and B are highly expressed does the K Factor activate. Either one alone, especially B expressed alone, could falsely damage normal tissue."
"We have designed a three-level verification step." Academician Chen brought up the details. "First level, vector binding; second level, intracellular environntal signal recognition after endocytosis; third level, the final vote of the micro gene circuit inside the cell nucleus. Only if all three levels are passed, the K Factor will express. Theoretically, the chance of false injury can be reduced to less than one in ten million."
"Theoretically!" Yang Ping repeated these three words, "Shen Guohua’s body can’t wait for theoretical errors. We need rapid validation through animal experints, but ti..."
"Use a humanized mouse model." Lu Xiaolu’s voice chid in, having just finished another analysis, "Transplant the cryopreserved tumor cell samples collected before Mr. Shen’s treatnt into immunodeficient mice to construct a personalized mouse model. At the sa ti, partially humanize the mouse liver to simulate his liver function status. Testing the new vector this way, while it can’t fully substitute for the human body, can predict safety and effectiveness to the greatest extent possible."
"What’s the model construction period?"
"Fastest is seventy-two hours." Lu Xiaolu said, "Our laboratory has mature processes that can be operated in parallel."
Yang Ping looked at Academician Chen, who nodded: "The preparation and purification of the dual-target vector, we’ll expedite, and within sixty hours, we can complete the laboratory-grade product, sufficient for animal experints and one human treatnt."
"Then let’s initiate." Yang Ping decided, "Professor Lu will be responsible for the animal model, Academician Chen will handle the vector, and we’ll be responsible for all testing coordination and contingency preparation. After seventy-two hours, based on the animal experint results, we’ll decide whether and when to conduct the second treatnt on Mr. Shen."
The tasks were subdivided, and the laboratory entered a high-speed operational state again. Everyone understood that this was not only about saving Shen Guohua but verifying a new technical route to cope with tumor adaptive resistance; its significance might be deeper than K Therapy itself.
Song Zimo walked to Yang Ping, and softly said: "Wu Changde’s press conference today was quite the spectacle. Open source, ecosystem, massive fund support, the combination of these words is very attractive."
Yang Ping’s eyes didn’t leave the gene map on the screen: "Don’t be distracted by public opinion, our only enemy is the disease, everything else is trivial."
"I’m worried..." Song Zimo wanted to remind Yang Ping.
Yang Ping looked away: "Vector virus, K Factor, target, these three combined seem simple, but achieving it is not as easy as they think; had it been easy, it would have been done long ago without waiting for them to join our open access program. The vector virus is manageable, K Factor is currently unique, and their so-called target is actually not the target we define; they only have the vector and a useless target, lacking the most important K Factor, they think we..."
They think our data was acquired in a year, so they can too, but they don’t know that to get these data in normal ti would take ten years.
Of course, these words were not spoken by Yang Ping, which is why Song Zimo was so worried.
...
Forty-eight hours later.
Inside Shen Guohua’s personalized humanized mouse model experint chamber.
Twenty mice, divided into four groups: control group, single-target A vector group, single-target B vector group, dual-target A/B vector group. Twenty-four hours after vector injection.
Single-target A group: tumor growth inhibition rate of 35%, but so mice showed mild elevation of liver enzys due to attacks on normal liver cells with low A receptor expression.
Single-target B group: tumor growth inhibition rate of only 15%, no significant toxicity because B receptor expression on the tumor was insufficient.
Dual-target A/B group: tumor growth inhibition rate of 68%! And no significant signs of liver or kidney toxicity! Pathology slices showed massive apoptosis of tumor cells, and a large removal of those purplish-blue adaptive resistant cells.
"Success!" a young researcher in Lu Xiaolu’s laboratory couldn’t help but exclaim softly.
But Yang Ping, Lu Xiaolu, and Academician Chen in the video link did not smile.
"Inhibition rate of 68%, very good, but 32% of tumor cells still survived." Yang Ping stared at the data, "Analyze the characteristics of the surviving cells."
More in-depth analysis quickly ca out: the surviving tumor cells showed a third evolution path—they simultaneously downregulated A and B receptors, switching to highly express a very rare receptor C, entering a kind of tabolic dormancy insensitive to the current immune attack.
"Escaped again." Song Zimo felt a chill, "Like playing whack-a-mole, knock down one, and it pops out from another hole, and this ti more cunning, it’s hiding."
"That’s a tumor." Yang Ping’s tone instead cald down, "If it could be completely eradicated so easily, it wouldn’t be a dical conundrum. Our dual-target attack this ti knocked out its main forces and first mutation troops, but its command tumor stem cells or highly heterogeneous cells have planned a second retreat and lurking strategy; tumor cells have their survival thods."
"Then what do we do? Design a three-target vector targeting receptor C?" Tang Shun asked.
"There’s no ti, and we might fall into an endless pursuit." Yang Ping shook his head, "We need to change our approach, not just rely on externally introduced specific killers but must maximize activation and arming of the patient’s own immune system, allowing it to continuously monitor and recognize constantly mutating tumor cells. This is the immune awakening enhancent plan we’ve been preparing."
He pulled up a long-prepared plan: "Simultaneously with dual-target vector therapy, use a combination of low-dose, ti-sequenced administration of immune modulators. The aim isn’t direct destruction but: to lift immune suppression in the tumor microenvironnt, break down defenses like PD-L1; train T cells and other immunocytes in the body to enhance their ability to recognize new antigens tumor mutation produces new proteins); change the local tabolic environnt the tumor relies on, making those dormant cells uncomfortable."
"It’s like...a combined campaign." Xu Zhiliang analogized, "Dual-target vector is...a precision airstrike, eliminating known main forces; immune modulation is...ground forces clearing and occupying, establishing long-term defense to deal with stragglers and new erging enemies."
"A good analogy." Yang Ping nodded, "Mr. Shen’s body is now the entire battlefield. Our previous treatnt was the airstrike. Now, ground forces need to go in. The risk is that immune modulation might trigger autoimmune reactions or excessive inflammation, requiring precise control of dosage and timing."
He looked towards Doctor Li Chao: "With Mr. Shen’s current liver function and overall status, assess the risk level of this combined sche."
Doctor Li Chao had studied the plan for a long ti: "Risk is high but controllable, provided our monitoring must be real-ti and precise."
"The wishes of the patient and family?"
"Ms. Zhou said her husband repeatedly said when he was conscious: keep moving forward, don’t look back."
Yang Ping closed his eyes, then opened them after two seconds, his gaze firm: "Initiate the combined treatnt plan."
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