CREATE Unveils Non-Viral Tech to Engineer Immune Cells In Vivo

CAMBRIDGE, Mass. – April 17, 2026 – In a move that could significantly reshape the landscape of cell therapy, CREATE Medicines today announced groundbreaking data on a novel platform capable of stably editing immune cells directly inside the body without using viral components. The presentations, set for the American Association for Cancer Research (AACR) Annual Meeting in San Diego, introduce the first in vivo evidence for RetroT, an all-RNA system designed for durable gene integration.

The clinical-stage biotech company is showcasing two key advancements that underscore its ambition to create scalable, off-the-shelf immunotherapies. The first is a multi-pronged approach that simultaneously engineers several types of immune cells to attack solid tumors. The second is the RetroT platform itself, a technology that promises the permanency of traditional gene therapy without some of its most persistent safety and manufacturing hurdles. These developments position CREATE at the forefront of the race to make powerful cell therapies more accessible and versatile for treating cancer and autoimmune diseases.

A New Path for Stable Gene Delivery

For years, the promise of CAR-T and other cell therapies has been tempered by significant challenges. The most common method, ex vivo engineering, requires removing a patient's cells, shipping them to a lab for modification with viral vectors, and then infusing them back—a costly, complex, and time-consuming process. While a new wave of companies is pursuing in vivo (in-body) engineering, most still rely on viral vectors or gene editing tools like CRISPR that create double-strand breaks in DNA.

CREATE's RetroT platform, detailed in a late-breaking abstract at AACR, offers a fundamentally different approach. Described as a first-in-class all-mRNA platform, RetroT aims to achieve stable and durable gene expression by integrating genetic code into the host cell's genome without using viruses or inducing potentially risky DNA breaks. This method could mitigate concerns over insertional mutagenesis associated with viral vectors and the off-target effects or chromosomal rearrangements linked to CRISPR-based editors.

The first in vivo data for this platform is compelling. In a leukemia model, CAR T-cells engineered using RetroT led to a significant reduction in tumor burden. This result serves as a critical validation, suggesting the platform can deliver on its promise of stable, long-lasting CAR expression—a key requirement for treating many cancers effectively. If proven safe and effective in humans, this non-viral, non-DNA-breaking method could represent a major leap forward in the safety and scalability of genetic medicine.

A Multi-Immune Attack on Solid Tumors

Beyond the novelty of its delivery system, CREATE is also pushing the boundaries of what in vivo therapies can target. While first-generation CAR-T therapies have shown remarkable success against blood cancers, solid tumors have remained a formidable challenge. Their complex and immunosuppressive tumor microenvironment (TME) often neutralizes single-pronged therapeutic attacks.

CREATE’s second AACR presentation directly addresses this problem by showcasing a strategy that engineers multiple immune cell types simultaneously. Using its established mRNA and lipid nanoparticle (LNP) delivery system, the company demonstrated the ability to program not only T cells but also Natural Killer (NK) cells and myeloid cells inside the body. This multi-immune strategy transforms the therapeutic paradigm from a single-soldier mission to a coordinated army assault.

In a preclinical colorectal cancer model, this approach drove tumor regression and, crucially, remodeled the hostile TME. By engineering myeloid cells—which can act as architects of the immune environment—the therapy appears to make the tumor more hospitable to an anti-cancer immune response. Meanwhile, the engineered T cells and NK cells launch direct attacks on the cancer cells. This ability to orchestrate a broader immune response in vivo could unlock effective treatments for a wide range of solid tumors that have resisted other immunotherapies.

Leading the In Vivo Race

The field of in vivo cell therapy is becoming increasingly crowded, with companies like Intellia Therapeutics, Kelonia Therapeutics, and Umoja Biopharma all developing platforms to generate therapeutic cells inside the patient. However, CREATE Medicines is leveraging its extensive clinical experience to carve out a leadership position. The company claims to have the largest human clinical dataset in the field, drawing on experience from over 50 patients and more than 200 administered doses across its Phase 1 studies.

This clinical validation, which has shown a manageable safety profile with no cumulative toxicities and evidence of activity—including one confirmed partial response lasting 16 months—provides a crucial foundation for its next-generation programs. "CREATE was built to rapidly iterate directly from our clinical data and unlock the clear advantages of in vivo cell therapy," said Robert Hofmeister, Ph.D., Chief Scientific Officer of CREATE. "The work we are presenting at AACR underscores this unique capability of our platform, leveraging our experience... to develop the next generation multi-immune CARs or stably integrated mRNA in vivo therapies."

This iterative, data-driven approach, combined with the technological differentiation of RetroT and its multi-immune targeting, positions the company as a formidable player. While competitors focus on in vivo delivery using CRISPR or lentiviral vectors, CREATE's all-RNA platform for stable integration represents a distinct and potentially safer path forward.

New Frontiers in Autoimmunity

The company’s ambitions extend beyond oncology. The same platform technologies are being aimed at autoimmune diseases, a therapeutic area where cell therapy is showing immense promise. The goal in autoimmunity is often to achieve an "immune reset" by eliminating the rogue B cells or T cells that attack the body's own tissues.

In February 2026, CREATE presented preclinical data from non-human primates demonstrating that its in vivo CAR-T platform could achieve complete B cell depletion with the potential for repeat dosing. This is a critical proof-of-concept for treating B cell-mediated autoimmune conditions like lupus or rheumatoid arthritis. An off-the-shelf, re-dosable therapy that can be administered in a standard outpatient setting would be a transformative option for millions of patients living with these chronic diseases.

The advancements being presented at AACR 2026, from the stable, non-viral integration of RetroT to the orchestration of multi-immune attacks, signal a significant maturation of in vivo cell therapy. By building on a foundation of human clinical data, CREATE Medicines is not just developing novel technologies, but is also charting a course toward making these powerful treatments a scalable and accessible reality for patients with cancer and autoimmune disorders. The data from San Diego this week will be closely watched as a potential glimpse into the future of immunotherapy.