Capítulo 1862: Chapter 1298: Carrier Replacent (Part 2)
But the issue arose during the animal experint phase: the mouse model showed that although the new vector had an inhibitory effect on pancreatic tumors, it unexpectedly caused mild inflammatory reactions in the liver and kidneys.
“Off-target toxicity.” Song Zimo gazed at the pathology slices, brows furrowed, “Although it’s not severe, it does exist. The vector may have recognized similar receptors with low expression levels in normal tissues.”
Tang Shun called up the receptor expression profile data: “This receptor is widely expressed during the fetal period, with only trace expression in a few tissues in adults. But our vector has too high an affinity, capturing even the trace expressions.”
Yang Ping stood in front of the whiteboard, which was filled with signal pathways and gene sequences. He had been working continuously for a whole day, yet his mind remained clear.
“As long as we can identify them and trigger the apoptosis program, that’s a victory. The remaining job is just continued improvent. We need to add a validation lock.” He drew a new gene circuit design, “If there’s no satisfactory single marker for the ti being, we can use two, allowing the vector to express the K Factor only when two markers are detected simultaneously. Tumor cells usually have multiple abnormal markers, while normal tissues rarely exhibit two at the sa ti.”
“But this will reduce infection efficiency.”
“Safety first.” Yang Ping put down the pen, “Efficiency can be optimized, but safety cannot be compromised. Redesign, resynthesis, revalidation.”
This ans at least a two-week delay, and that pancreatic cancer patient might not be able to wait two weeks.
At that mont, the laboratory door opened, and Lu Xiaolu walked in, followed by a gentleman in his sixties with an elegant deanor.
“Professor Yang, sorry to disturb you so late.” Lu Xiaolu said, “This is Academician Chen Yongnian from Tsinghua University, an expert specializing in adenovirus vectors. We’ve often discussed challenges together before. He ca over specifically after looking at so of our published data; he has so ideas he wants to discuss with you.”
Yang Ping was sowhat surprised. Academician Chen is an authority in dostic viral vector research but has always focused on basic research, rarely involving clinical translation.
“Professor Yang, it’s a pleasure to et you.” Academician Chen extended his hand, “I’ve noticed your precision in the targeted strategy design, but one detail caught my attention. You’re using adenovirus serotype 5, which is the most common, but also the most likely to be cleared by preexisting human immunity.”
Yang Ping imdiately understood his point: “You an so patients might have antibodies from previous infections with adenovirus serotype 5, leading to premature vector clearance and affecting efficacy?”
“Exactly! And this issue varies greatly among different ethnic groups.” Academician Chen presented unpublished data from his team, “We studied the adenovirus antibody profiles in East Asian, European, and African populations. The serotype 5 adenovirus neutralizing antibody positivity rate is about 40% in the Chinese population, reaching 60% in Europe, and in so regions of Africa, even over 80%.
This data left everyone in the laboratory stunned. If true, it would an that more than half of the European patients might have preexisting immunity to the K Therapy vector, significantly reducing its efficacy.
“Then the previous… European patients… treatnt data…” Xu Zhiliang hesitated.
“May have unintentionally excluded patients with high-titer antibodies.” Academician Chen said, “If multiple treatnts are needed in the future, this problem will beco more pronounced.”
Yang Ping quickly accessed the European Center’s patient data and indeed discovered a pattern: all the patients with effective treatnt had low levels of adenovirus neutralizing antibodies prior to treatnt.
“We overlooked this issue.” Yang Ping objectively admitted, “We were always focused on targeting but overlooked the basic immunological characteristics of the delivery vector itself.”
“This isn’t your issue because you wouldn’t spend much energy researching the vector virus; you have to apply mature vector viruses. The vector virus is our area of expertise. Before our data appeared, the adenovirus you chose was undoubtedly the best, but now things are different, which is why I’m offering a solution.” Academician Chen opened his laptop, “Our laboratory developed a ‘adenovirus serotype mixed vector library’ technology. Simply put, it constructs multiple different serotype vector versions for the sa therapeutic gene. Prior to treatnt, we detect the patient’s antibody profile and choose a serotype vector for which the patient has no antibodies for personalized delivery.”
The screen displayed gene modification sches for twelve different adenovirus serotypes, each tailored with a K Factor expression cassette.
“This requires a huge production system and complex detection processes.” Song Zimo said.
“But it solves the fundantal issue.” Yang Ping had already picked up a pen and started calculating, “Moreover, if combined with the dual-marker validation lock we just designed, safety and efficacy can both be significantly elevated.”
Yang Ping began integrating Professor Chen’s new technology for analysis, and they all started re-discussing the vectors.
Unconsciously, it was already midnight, and the preliminary cooperation plan was finalized: Academician Chen’s team would provide serotype modification technology and a mixed vector library, the Sanbo team would handle the integration of the targeting system and clinical translation, both parties sharing intellectual property and advancing together.
“This could be our chance to overco the greatest technical bottleneck.” Song Zimo said.
“But also our greatest challenge.” Yang Ping rubbed his temples, “It ans retrofitting all production lines, updating all training content, revising all clinical protocols, practically starting from scratch.”
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