Building the Future of Cell Therapies: Insights From Dr. Andrew Mancini
The field has changed a lot since 2017.
Complete the form below to unlock access to ALL audio articles.
As the field of engineered ex vivo cell therapies continues to progress, significant advancements are occurring in both the complexity and diversity of these therapies.
Presenting at Technology Networks’ Cell and Gene Therapy 2025 Symposium, Dr. Andrew Mancini, a cell engineering scientist and senior corporate development manager at MaxCyte, shared his insights on how engineered cell therapies have evolved over the past eight years and what lies ahead for the next decade.
Reflecting on the past: From simplicity to complexity
Mancini began by examining the state of cell therapies in 2017. He described a relatively straightforward process in which a cell engineer would get “started with a patient with a hematological malignancy, isolated CD3-positive T cells, which you then transduced with a CAR (chimeric antigen receptors) lentivirus, so you could stably express your CAR sequence.”
What are CD3 cells?
T cells are distinguished by the presence of the T-cell receptor and the cluster of differentiation 3 (CD3), which are found on all T cells, regardless of their role. T cells can further be categorized into subtypes by the expression of other markers including CD4 and CD8.
This approach, common in 2017, was based on the use of autologous T cells and lentiviral transduction.
Fast forward to 2025, and the field has seen tremendous change. The diversity of starting materials, for one, has expanded dramatically. While T cells remain the most common starting material, Mancini noted that “natural killer (NK) cells and induced pluripotent stem cells (IPSCs) are the number two and number three most common cell types.”
What are NK cells?
NK cells do not mediate graft-versus-host disease and can be easier to use in an allogeneic setting.What are IPSCs?
IPSCs are non-cancer cells that can continue to divide indefinitely in a culture dish and retain the ability to give rise to every cell type in the body, making them invaluable in cell therapy research.Moreover, Mancini pointed out that “45% of all engineered ex vivo cell therapy products in development do not use T cells as the starting material.”
Non-viral engineering and the emergence of new cell types
One of the most striking developments in the past eight years has been the transition from viral to non-viral engineering strategies.
In 2017, “over 90% of engineered cell therapies used a single lentiviral transduction step,” according to Mancini. Now, however, non-viral strategies have seen a surge, with “38% of engineered ex vivo cell therapy products in development using one or more non-viral steps.”
Mancini emphasized that the adoption of technologies like CRISPR-Cas9 and other nucleases has played a key role in this shift: “We see that for every new viral-only product that enters development, there are nearly two new non-viral or hybrid products entering development at the same time.”
The rise of allogeneic therapies
Another significant shift in the field is the move toward allogeneic therapies, where cells are derived from a donor instead of the patient.
“In 2017, about 90% of engineered therapies were autologous,” Mancini told the Technology Networks audience. “In 2025, we see a much stronger shift towards allogeneic approaches, with nearly half of all therapies now being allogeneic.”
This shift is driven by the challenges faced by autologous therapies, including high costs and complex manufacturing processes. Allogeneic therapies, Mancini believes, could provide a more scalable and cost-effective alternative to autologous products, which require individualized production.
Transient cell therapies: A growing trend
One of the more innovative strategies Mancini discussed was the rise of transient cell therapies. Unlike traditional autologous approaches that make permanent changes to a cell’s genome, transient therapies involve temporary modifications, such as transiently expressing CAR through mRNA.
Mancini acknowledged that while transient therapies are still a small minority of the field, they are growing rapidly: “I anticipate that by 2030, transient autologous therapies could represent probably close to a quarter of all autologous cell therapies in development.”
The ability to create therapies that don’t permanently alter the genome could lead to more flexible, faster manufacturing and lower costs, offering promising benefits for both developers and patients.
A future of increasing complexity
Looking forward to 2035, Mancini predicted that cell therapy will continue to become more complex.
Creating Space in Science: LGBTQIA+ Voices on Belonging in Pharma
In this listicle, LGBTQIA+ scientists offer insights into how inclusion can be built into everyday lab culture, from normalizing pronoun sharing and celebrating diverse holidays to rethinking policy and representation.View Listicle
“I believe that ex vivo cell therapy is going to stay highly complex,” he said, citing the growing toolkit available to researchers. “I think we are still at the beginning of cell therapy complexity.”
However, increased complexity brings challenges.
“With more complexity comes typically more risk of manufacturing failures and also higher manufacturing costs,” Mancini warned. He stressed the importance of accurately characterizing engineered cells, especially as more engineering steps are incorporated into cell therapy processes.
Navigating complexity: Strategies for success
As the field advances, Mancini highlighted the importance of embracing complexity while managing the associated risks. One key strategy he advocated, is to “start with the finish” – meaning, choosing the right tools and platforms from the outset to avoid costly changes during later stages of development.
He also discussed the importance of “leaving no stone unturned” in the development process, recommending that developers thoroughly understand and characterize every aspect of their therapies.
“The more you can learn about the product earlier, the less chance you’re going to be surprised later,” he advised.
The road ahead for cell engineered cell therapies
Mancini concluded by emphasizing that, while complexity in engineered cell therapies is here to stay, this complexity presents incredible opportunities to improve patient outcomes.
“The cell therapy developers who can embrace this complexity while mitigating risk will be the most successful,” he said. “These developers will be able to produce truly amazing cell therapy products over the next 10 years.”
As cell therapy evolves, Mancini's insights paint a picture of a future that is more diverse, more complex and ultimately more promising for patients and developers alike. The continued integration of innovative technologies, such as CRISPR, non-viral delivery systems and transient therapies, will shape the landscape of cell therapy for years to come.
This content includes text that has been generated with the assistance of AI. Technology Networks’ AI policy can be found here.
