The Emergence of In Vivo CAR-Tumor: A Disruptor in Immune Cell Therapy-TONACEA

The Emergence of In Vivo CAR-Tumor: A Disruptor in Immune Cell Therapy

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2026-04-09 09:15

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Dr. Zhou Guoqing, Founder and CEO of Shanghai Rongrui Pharmaceutical, stated: “I often let my soul drift in the boundless starry sky in the dead of night, overlooking the entire Earth, and agonizingly question myself: We have invested enormous human, material and financial resources in the vast ocean of immune cell therapy—from autologous and allogeneic therapies to the currently red-hot in vivo cell therapies such as In Vivo CAR-T.”

“Yet to date, we have only achieved limited efficacy and incurred exorbitant costs in the treatment of solid tumors. How much farther must we go? Have we been led astray from the course of human civilization by esteemed pioneers? Is it now time to correct that course?”

“Yes, the era of In Vivo CAR-Tumor has arrived.”

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Directly Engineering Tumor Cells: Equipping Tumor Cells with Anti-Tumor Targets

On the crowded track of tumor immunotherapy, the vast majority of companies focus on developing targeted drugs around keywords including T cells, PD-1, and CAR-T. But what if patients lack these targets?

“I have asked many targeted drug developers this question, and not a single one could answer me,” Dr. Zhou recalled. During his years working in biopharmaceutical investment in New York, he engaged with numerous innovative US pharmaceutical companies daily, nearly all of which told the same story: identify a target, develop a targeted drug, and strike tumors precisely. “Targeted drugs are like missiles, and tumor antigen targets are GPS coordinates.”

This logic is theoretically flawless, yet it has a fundamental flaw in clinical practice: not all tumor patients have actionable targets. Even when targets exist, the abundance and heterogeneity of tumor antigens render single-target drugs unable to completely eliminate all cancer cells. After treatment, tumor cells with targets are killed, while those without survive, often leading to drug resistance, recurrence, and ultimately no available treatment options.

Faced with this dilemma, Dr. Zhou adopted a simple yet bold approach: since tumor cells lack targets, proactively equip them with targets inside patients’ bodies; since ex vivo exogenous drugs struggle to efficiently reach tumor sites, let patients’ own tumor cells produce anti-tumor drugs.

“Based on first principles, direct problems demand direct solutions.” In 2018, Dr. Zhou founded Joint Biosciences in the United States, and established Rongrui Pharmaceutical in Shanghai in 2020, with the mission of directly engineering tumor cells.

Today, the OVV-01 therapy born from this concept has entered Phase II clinical trials in both the US and China, and has been granted Fast Track designation by both the US FDA and China’s NMPA. No other company worldwide has advanced a comparable candidate into clinical trials.

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World’s First Innovation: Tumor Cells as Anti-Cancer Factories

The foundation of OVV-01 therapy is the vesicular stomatitis virus (VSV) vector platform, developed by Rongrui Pharmaceutical over years of research, which also serves as its core technological barrier.

VSV is inherently highly tumor-specific. In normal cells, it is rapidly inhibited by the human type I interferon pathway and cannot replicate. In tumor cells, however, defects in the type I interferon pathway allow the virus to replicate efficiently, with in vivo infection titers reaching over a thousand-fold. Moreover, this virus poses virtually no threat to humans, only causing non-fatal oral blisters in animals such as pigs, cattle, and horses.

Yet identifying a suitable virus was only the first step.

Starting in 2017, the R&D team spent a full three years stabilizing this RNA virus to a clinically usable level. RNA viruses are inherently prone to mutation, requiring structural stabilization to enable insertion of foreign genes. After countless failures, they finally achieved stability far exceeding FDA requirements.

Leveraging this viral vector system, Rongrui Pharmaceutical has established a unique dual-delivery platform for “antigen targets + bispecific/trispecific/multispecific antibodies”, enabling tumor cells to produce both anti-tumor antigen targets and antibodies— the key to making tumor cells “self-produce and self-destruct”.

Through this system, researchers can precisely localize tumor antigens on the extracellular or intracellular membrane of patients’ tumor cells, making them recognizable to the immune system. Meanwhile, gene sequences for bispecific or trispecific antibodies are integrated into the viral vector. Once the virus enters tumor cells, the cells produce antibodies on their own. These antibodies automatically recognize and attack antigens on their own membrane, triggering “autophagic” killing.

“A patient’s tumor cells act as a production factory, and the antibodies they generate eliminate tumors locally,” Dr. Zhou vividly explained. “Furthermore, a single tumor tissue contains cancer cells at different stages of development, progression, and evolution, each with distinct functional characteristics and tumor antigen targets. Traditional anti-tumor targeted drugs launch single-stage, single-target, single missiles, while we launch dozens of multi-stage, multi-target missiles simultaneously, covering multiple targets across all tumor stages. This leaves cancer cells at every stage with nowhere to hide.”

The significance of this technological platform lies not only in its innovative mechanism of action, but also in its complete circumvention of classic dilemmas in tumor therapy. Since antigens and antibodies are delivered by the same viral vector, physicians do not need to screen patients for specific targets before treatment. Any tumor patient, regardless of cancer type, stage, or target expression status, can receive this therapy.

Following genetic modification, OVV-01 replicates and lyses tumor cells specifically without damaging normal cells. It also functions as a therapeutic vaccine, inhibiting tumor metastasis and recurrence, promoting T-cell activation, and forming a closed “lysis-sensitization-killing” loop to achieve long-term tumor control.

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Activating a Systemic, Coordinated Anti-Cancer Defense: Multi-Targets and Multiple Administration Routes

Traditional oncolytic viruses are administered via intratumoral injection. Beyond its multi-target advantage, Rongrui Pharmaceutical has pioneered the “intratumoral + intravenous” combined administration route globally, and is the only company worldwide to receive approval for this delivery method from both the US FDA and China’s CDE for viral oncology drugs. This innovative administration route enables full-body, “no-blind-spot” coverage of tumors.

Dr. Zhou explained that tumor growth in any part of the body results from comprehensive systemic responses. The tumor site is not merely the area with the weakest immune function. Different administration routes activate distinct bodily systems, including the immune system. Only a combination of multiple routes can mobilize the body’s full anti-cancer potential.

The team has since expanded administration routes to 11, including intratumoral, intravenous, subcutaneous, intramuscular, intracranial, intrathecal, intraperitoneal perfusion, and intravesical instillation. Physicians can flexibly select routes based on tumor location, achieving precise delivery to tumors across the body while stimulating comprehensive responses in the skin, muscles, nerves, and other systems to form a coordinated systemic anti-cancer defense for more effective tumor elimination.

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Ten Years of Perseverance: Making Tumors “Commit Suicide”

Dr. Zhou’s decade-long commitment stems from a heartfelt anti-cancer mission born of regret.

During his doctoral studies, his closest cousin was diagnosed with liver cancer during a premarital checkup and passed away just two weeks later. “This was a devastating blow. From that moment on, I vowed to develop new drugs for tumor treatment, and for decades I have sought breakthroughs in this field.”

Warmth and conviction shine in Dr. Zhou’s eyes. His professional background embodies cross-disciplinary innovation. A molecular biologist by training, he was already an industry pioneer during his doctoral and postdoctoral research.

In the 1990s, while most researchers focused on single disciplines, he broke the boundaries of animal and plant genes, completing the first study transferring peptide genes for antimicrobial resistance from animals into plants for production, with findings published in top academic journals.

His research scope continued to expand across multiple biotechnology fields. He developed eye drops targeting drug-resistant bacteria by integrating specific genes for antibacterial effects, and explored applications in anti-infective therapies. In the 1990s, he also combined heat shock proteins with HPV antigens to develop immunotherapeutic drugs as therapeutic cervical cancer vaccines, and founded his first company.

His experience in New York as a biotech investor from 2014 to 2019 allowed Dr. Zhou to move beyond the laboratory and identify real pain points in drug R&D and clinical treatment. During this period, he visited hundreds of US oncology drug developers, all focused solely on targeted tumor therapies—yet none could answer the question: what to do for patients without actionable targets?

This observation led him to question whether existing drug development strategies left blind spots for patients lacking targetable sites.

In 2017, Dr. Zhou officially launched R&D for this technology in the US, marking the start of Rongrui Pharmaceutical’s innovative journey.

Currently, OVV-01 is in Phase II clinical trials, making Rongrui Pharmaceutical the first company worldwide to advance “tumor cell antigen target loading” to Phase II. It has obtained approval for nine solid tumor indications, including common cancers such as non-small cell lung cancer and colorectal cancer, as well as several rare small tumors. It has been granted Fast Track designation by both the China CDE and US FDA, and received a Phase I clinical waiver from both agencies, with Phase II trials underway in both China and the US.

Concurrently, Rongrui Pharmaceutical has launched multiple IIT clinical collaborations with top oncology hospitals in the US and China to develop life-saving therapies for patients.

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No Global Comparables: What Empowers This Chinese Biotech?

In the early days of entrepreneurship, when pitching to investors, Dr. Zhou was frequently asked an awkward question: “Which US company is your comparable?” He admitted this posed significant challenges during fundraising.

With no global peers pursuing the same technical path, investors struggled to evaluate the project’s technological value and market potential. He observed that roughly 90% of funds hesitated upon first contact.

Only in recent years have several US companies emerged with similar approaches—using viruses to express tumor antigens combined with personalized cell therapies such as CAR-T. However, these companies remain in the preclinical stage, putting Rongrui Pharmaceutical at least five years ahead in development.

In the domestic market, despite intense competition in tumor immunotherapy, nearly all players focus on mainstream technologies including CAR-T, PD-1, and ADC. No other company has followed Rongrui Pharmaceutical’s pioneering “tumor cell engineering” pathway.

From a technological barrier perspective, this approach relies on multiple critical steps: screening and stabilization of viral vectors, efficient loading and expression of foreign genes, design and screening of multi-target antibodies, and clinical validation of multiple administration routes. Each step demands long-term technical accumulation and extensive experimental data. Even for latecomers, building corresponding capabilities will take years.

Several US and international pharmaceutical companies have actively sought partnerships with Rongrui Pharmaceutical for tumor target loading. “US firms are approaching us to load targets, and we are in discussions. We will first achieve breakthroughs, then consider large-scale licensing.”

Dr. Zhou is unconcerned about potential imitators. He believes a technological track requires sufficient participants to attract sustained capital and talent, driving industry-wide progress. “A single tree cannot form a forest.” He hopes more companies will join this field to expand the sector together.

Rongrui Pharmaceutical has established in-depth partnerships with multiple leading domestic pharmaceutical companies, including Akeso Biopharma. The company is also expanding its global patent portfolio, with core technologies already granted numerous international and domestic patents.

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A New Journey and the Next Breakthrough Frontier: The Emergence of In Vivo CAR-Tumor, Disrupting Immune Cell Therapy

“This technical term cannot be found online,” Dr. Zhou noted. “We coined this name.”

Building on past achievements, the team has disrupted existing cell therapies and opened a new journey and the next breakthrough frontier. Current immune cell therapies (including CAR-T, UCAR-T, and In Vivo CAR-T) face insurmountable limitations of low efficacy and high costs. Leveraging the tumor-specific VSV viral delivery system, the team has pioneered the disruptive technology of In Vivo Chimeric Antigen Receptor Tumor Cell Therapy (In Vivo CAR-Tumor).

Dr. Zhou posed a fundamental question: the core goal, the first principle of immune cell cancer therapy, is to kill cancer cells.

“Why do we frantically modify immune cells of the immune system—punching holes in T-cell membranes, installing CARs, and sending them to attack cancer cells—instead of directly punching multiple holes in cancer cell membranes, installing CARs, and letting T cells attack them ferociously? The former actually damages the immune system, nature’s most powerful anti-cancer defense forged over billions of years of evolution, while the latter is the logical choice.”

In Dr. Zhou’s view, the root cause of tumor cells evading immune surveillance—the first principle problem—is not a defect in the immune system itself, but tumor cells disguising themselves to avoid immune recognition.

He argues that instead of impairing the cancer-killing immune system, we should directly resolve the issue of immune evasion: equip tumor cells with CARs, just as we previously equipped them with antigen targets, allowing immune cells to directly attack and kill cancer cells. This is the philosophy guiding their drug development.

“Thus, In Vivo CAR-Tumor was born.”

In Vivo CAR-Tumor stands alone as a technology, representing both challenge and immense definitional power.

If validated commercially, the VSV-based precision targeted delivery system and In Vivo CAR-Tumor are poised to become a new technical branch in tumor immunotherapy. As the founder of this branch, Rongrui Pharmaceutical will own the definitional rights to the track, pioneer the next breakthrough frontier in cell therapy, and offer new hope to cancer patients worldwide.

“Life is full of challenges—and challenges make it extraordinary!” Determination glints in Dr. Zhou’s eyes once more. His story is that of a Chinese drug developer committed to relentless innovation and perseverance, much like all entrepreneurs.

In Vivo CAR-Tumor: the next frontier of cell therapy. An endless frontier, an endless challenge, an endless hope, leaving boundless thoughts and possibilities for the future…

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