Designing Next-Generation Cell Therapies: From Immune Recognition to Engineered Precision at South Korea’s 4th CGT Congress

On the opening day of the 4th Cell & Gene Therapy Innovation & Access Congress Asia in Seoul, discussions moved quickly past familiar narratives of promise and into a more exacting question: how to design cell therapies that behave predictably in complex biological systems—and remain controllable as they move toward clinical and manufacturing scale.

As the broader cell and gene therapy field enters a phase of maturation, the sessions underscored a shift away from incremental optimization toward a more fundamental rethinking of how therapies are engineered, validated, and ultimately understood.

Making Tumors Visible—Francesco Marincola on Viral Mimicry and “Cancer Dark Matter”

In one of the day’s central keynote presentations, Francesco Marincola, Chief Scientific Officer and Global Head of Research at Translational and Advanced Medicine (TAM), reframed how the immune system recognizes cancer.

Rather than positioning immunotherapy as an external intervention, Marincola described how tumors themselves can generate the signals required to trigger immune activation. Through epigenetic dysregulation, cancer cells produce nucleic acids and peptides that resemble those of virus-infected cells—a process known as viral mimicry. This activates innate immune sensors while simultaneously generating neoantigens, making tumors visible to immune surveillance.

He paired this with the concept of “cancer dark matter”—previously unrecognized antigenic elements emerging from non-canonical transcriptional activity. Together, these mechanisms suggest that the most effective therapies may not be those that force immune responses, but those that amplify signals already embedded within tumor biology.

The relevance for current development pipelines is immediate. As tools such as single-cell sequencing, epigenomic profiling, and AI-driven antigen discovery mature, they are no longer simply analytical layers—they are becoming foundational components of therapy design. This shifts immunotherapy from forcing recognition to refining it, placing greater importance on identifying signals that can be consistently reproduced across patients.

Standardizing Living Systems—Masahiro Kino-oka on Robotic Manufacturing

If Marincola addressed how therapies should interact with biology, Masahiro Kino-oka, Professor at Osaka University, focused on how those therapies can be produced without losing integrity.

Kino-oka presented an automated manufacturing platform for iPSC-derived cells that replaces manual intervention with robotic systems capable of media exchange, morphological monitoring, and autonomous subculturing. His data showed that automation can match—or exceed—expert manual protocols while significantly reducing variability.

In cell and gene therapy, manufacturing is not a downstream consideration—it defines the product itself. By embedding control into automated systems, manufacturing begins to shift from a variable process to a defined, reproducible framework—one that determines whether therapies can ultimately scale beyond specialized settings.

Engineering Immune Cells for the Real World

Across the congress, a consistent theme emerged around redesigning cell therapies to function under real-world constraints.

Andy Tan (Bioprocessing Technology Institute, A*STAR) addressed one of the most immediate barriers in NK cell therapy: cost. By engineering feeder cells to express membrane-bound cytokines, his approach reduces reliance on soluble cytokines, which are both expensive and difficult to control at scale. This reflects a broader move toward embedding efficiency directly into biological systems rather than relying on external process optimization.

Shin-Il Kim (ViGenCell) extends this logic further. His work on genome-edited CAR-iPSC-NK cells combines induced pluripotent stem cell platforms with precise genetic engineering to produce uniform, off-the-shelf cell therapies. By standardizing both the cellular starting material and the engineering process, this approach aims to reduce variability while improving persistence and safety.

Together, these strategies point to a structural shift: cell therapies are no longer designed solely for efficacy, but for manufacturability, reproducibility, and regulatory alignment from the outset.

Expanding the Therapeutic Toolkit: From Secretomes to Metabolic Reprogramming

Several speakers highlighted how the definition of cell therapy itself is expanding—both toward simplification and increased complexity.

Sandy Qlintang (Dhyana Pura University / PT BiFarma Adiluhung, Kalbe) presented a cell-free approach using UCMSC-derived secretomes formulated into a topical gel. By leveraging paracrine signaling rather than live cells, this strategy bypasses many of the logistical and regulatory challenges associated with cell-based therapies, offering a more accessible model for tissue regeneration.

At the other end of the spectrum, Xiaotong Song (Texas A&M University / Cellula Biopharma) introduced metabolically reprogrammed CAR-T cells designed to overcome the suppressive tumor microenvironment in solid cancers. By integrating ADA1, CD26, and IL-15, these engineered cells enhance mitochondrial function, resist immunosuppressive signaling, and sustain long-term activity.

Taken together, these approaches expand the field in two directions—toward streamlined, cell-free systems on one end, and increasingly sophisticated, multi-layered cellular engineering on the other. This divergence reflects a broader strategic shift: developers are no longer optimizing for a single modality, but for how different approaches can balance efficacy, scalability, and clinical feasibility within real-world constraints.

Precision Engineering Meets Clinical Reality

Across multiple presentations, a consistent pattern emerged: advances in molecular tools are directly shaping not just discovery, but functional therapeutic performance.

Yi Tian Ting (Monash University) demonstrated that CRISPR-based receptor replacement in regulatory T cells can significantly improve antigen-specific immunosuppression compared to traditional lentiviral approaches, highlighting how editing strategy directly impacts therapeutic precision.

Mihue Jang (Korea Institute of Science and Technology) explored CAR-NK approaches targeting cancer-associated fibroblasts, while also using mRNA-based CAR constructs to accelerate screening and optimization workflows.

Meanwhile, Patrick Tang (Chinese University of Hong Kong) applied single-cell sequencing and AI-driven analysis to identify previously uncharacterized immune cell populations in non-small cell lung cancer, linking discovery platforms directly to therapeutic targeting strategies.

Across these efforts, tools such as CRISPR, mRNA engineering, single-cell sequencing, and computational modeling are no longer isolated technologies. They form an integrated toolkit for designing therapies that can function reliably within complex biological systems. Their convergence is critical: by linking precise genetic control with predictive analytics and real-time cellular insight, these tools enable therapies to be engineered not just for efficacy, but for consistency, safety, and scalability in clinical settings.

From Development to Deployment: Designing for Scale from the Start

While discovery dominated the track, several sessions underscored the importance of aligning early design decisions with downstream realities.

Antonio Lee (Medipost) presented the commercialization pathway of CARTISTEM®, an allogeneic stem cell therapy for osteoarthritis that has already treated more than 36,000 patients in Korea. His experience highlighted that clinical success depends not only on efficacy, but on the integration of manufacturing infrastructure, regulatory strategy, and long-term scalability.

Similarly, Frederick Derosier (Fortrea) emphasized that early clinical trial design—particularly first-in-human studies—must anticipate global development pathways, rather than optimizing solely for initial approval.

These perspectives reinforce a critical shift: translation is not a later-stage challenge, but a design constraint from the beginning. In practice, this means therapeutic development is increasingly shaped by manufacturability, regulatory alignment, and clinical usability from the outset, rather than being retrofitted after proof of concept.

A Field Redefining How Therapies Are Built

By the end of Day 1, a pattern had emerged. The CGT field is no longer defined by isolated breakthroughs, but by how effectively it integrates multiple layers of development into a coherent system.

Biological insight, engineering tools, manufacturing systems, and clinical strategy must now function together—not sequentially, but simultaneously.

What distinguishes the current moment is not the emergence of any single technology, but the recognition that therapies must be designed with their full lifecycle in mind. From the earliest stages of discovery, decisions are increasingly shaped by how well they can be translated, reproduced, and delivered at scale.

In that sense, the next generation of cell therapy is not defined by a platform, but by an approach—one that treats biology, engineering, and systems design as inseparable. And it is this approach that is now beginning to define the field.

Author

Bernice Lottering