The Rise of Allogeneic Cell Therapies: Strategies, Challenges, and Clinical Advances

Apr 8, 2025

As proteins and enzymes for cell therapy continue to revolutionize the treatment landscape for cancer and hereditary diseases, the field is shifting its focus from personalized, autologous approaches to scalable, off-the-shelf allogeneic solutions. This transition brings new opportunities and inevitable new challenges. Therapeutic developers in the advanced therapy field are actively exploring various options to advance universal cell therapies into clinical stages. This includes using alternative immune cell types and implementing precise gene editing strategies. Here, we discuss an overview of the current trends of allogeneic cell therapy, highlighting the key technology platforms, ongoing clinical programs, and also the gene editing technologies that empower allogeneic cell therapies.

KACTUS is proud to support cell therapy process development and manufacturing with a high-performance base editor and Cas9 enzyme.

Autologous vs. Allogeneic Cell Therapy

Autologous chimeric antigen receptor T-cell (CAR-T) therapy is a “vein-to-vein” live cell therapy, which minimizes the risk of immune rejection. Currently, all FDA-approved CAR-T cell therapies follow the autologous treatment pathway. This involves collecting the patient’s own cells as the starting material, engineering them ex vivo to express the CAR on the cell surface, expanding them, and reinfusing them back into the patient. Some patients, however, cannot benefit from this therapeutic scenario due to difficulties in cell collection or poor cell quality. Additionally, the high manufacturing costs and long production timelines limit the widespread adoption of autologous CAR-T therapy.

Allogeneic CAR-T therapy, on the other hand, is an “off-the-shelf” type of cell therapy. It collects cells from healthy donors to manufacture cell products that can be used for multiple patients in a single production run. Each batch can potentially serve dozens or even hundreds of patients. Compared to autologous therapies, this approach overcomes limitations related to starting material and production time, enabling on-demand usage and offering a feasible solution to the challenges of autologous CAR-T therapy.

Advantages and Challenges of Allogeneic CAR-T cell therapy

Allogeneic CAR-T therapy overcomes the limitation of using autologous cells, offering a new treatment option for patients who cannot provide qualified cells. Its “off-the-shelf” nature shortens the traditional one-month manufacturing timeline of autologous therapies, offering on-demand availability. Additionally, large-scale production can significantly reduce the final costs and increase accessibility.

However, allogeneic cell therapy also faces certain limitations. The major risks for allogenic therapy stem from host-mediated graft rejection and graft-versus-host disease (GvHD). The host immune system recognizes donor cells’ MHC molecules and rapidly eliminates the CAR-T cells. This shortens the persistence of CAR-T cells in the patient’s body, leading to reduced efficacy. Moreover, donor CAR-T cells will also attack host tissues, causing symptoms in the skin, liver, and gastrointestinal tract, and potentially leading to multi-organ damage that can be life-threatening. Fortunately, these risks can be effectively minimized through genetic engineering of cell products (Figure 2) or by using other types of immune cells (Table 1). These cell types offer unique immunological features that can reduce the need for extensive gene editing or avoid GvHD at the source.

Figure 2. Genetic modifications required for various off-the-shelf CAR cell products. Nat Rev Clin Oncol 22, 10–27 (2025) [1].

Alternative Cell Type	Potential Advantages	Potential Disadvantages	Representative Companies & Pipelines
γδ T Cells	Low risk of GvHD, no need to disrupt TCR, may require less gene editing	Represent only a small fraction of peripheral T cells; difficult to isolate and expand; uncertain efficacy compared to CAR-T therapies	Adicet Bio, ADI-001 (targets CD20)
UCB-Derived T Cells	Relatively easy to obtain, no need to collect peripheral blood lymphocytes	Requires HLA matching	UCELLO, UC101 (targets CD19)
NK Cells	Low GvHD risk, abundant in peripheral and cord blood, multiple cytotoxic mechanisms, lower toxicity in current clinical data	Prone to exhaustion, difficult to transduce, risk of rejection, short-lived without cytokine support	Wugen, WU-NK-101
iPSC-Derived Cell Types	Can differentiate into various cell types, more amenable to multiplex editing and storage	Immature cell phenotypes may limit efficacy	Fate Therapeutics, FT819 (targets CD19)

Table 1. Alternative cell types for CAR-based cell therapy

Clinical Advances of Gene Editing Fueling Allogeneic Cell Therapy

While selecting the right cell type is critical for minimizing GvHD risk and enhancing compatibility, gene editing serves as a more powerful strategy to fine-tune these cells for therapeutic use. Regardless of the starting cell—whether T cells, NK cells, or iPSC-derived cells—precise genome modifications can eliminate immunogenicity, enhance function, and support large-scale, off-the-shelf manufacturing. Technologies such as CRISPR-Cas9, base editing, prime editing, and epigenetic editing are accelerating the development of universal cell therapies and are now advancing into clinical trials. Supporting these technologies often requires specialized custom protein expression to produce engineered enzymes or tailored gene editing components that meet precise research and clinical specifications. This marks a new era in engineered cell therapies for cancer, genetic disorders, and infectious diseases. Examples include:

Beam Therapeutics has initiated a Phase I/II clinical trial for Beam-201, a CAR-T therapy targeting CD7 in T-cell leukemia and lymphoma. The therapy uses base editing to knock out the expression of CD7, TRAC, CD52, and PDCD1 on T cells, aiming to enhance the allogeneic compatibility of CAR-T cells [2].
Base Therapeutics developed NK510, a gene-edited NK cell therapy using single-base editing technology. In 2024, NK510 received clinical approvals in the U.S. for the treatment of advanced solid tumors. The therapy uses the protein-based base editor Accubase® to edit NK cells in vitro [3].
On April 9, 2024, Prime Medicine announced that its prime editing therapy for treating chronic granulomatous disease (CGD) has received FDA approval for an IND application and will proceed to a global Phase 1/2 clinical trial [4].
In November 2024, Epigenetic Medicine received CTA approval from New Zealand’s Medsafe and the Health and Disability Ethics Committees (HDEC) for EPI-003, an epigenetic editing therapy targeting chronic hepatitis B caused by HBV (5).

Company	Products	CAR	Cell Source	Gene-editing Tools	Gene-editing Strategy	Phase
Poseida (acquired by Roche)	P-BMCA-ALL01	BCMA	T cell	Cas-CLOVER	KO TRBC and B2M	Phase I
Poseida (acquired by Roche)	P-CD19CD20-ALL01	CD19/CD20	T cell	Cas-CLOVER	KO TRBC and B2M	Phase I
Allogene Therapeutics	cema-cel	CD19	T cell	TALEN	KO TRAC and CD52	Phase II
Allogene Therapeutics	ALLO-316	CD70	T cell	TALEN	KO TRAC and CD52	Phase I
Wugen	WU-CART-007	CD7	T cell	CRISPR	KO TCR and CD7	Phase I
Wugen	WU-NK-101	/	NK cell	N/A	N/A	Phase I
Adicet Bio	ADI-001	CD20	γδT cell	N/A	N/A	Phase I
Caribou Biosciences	CB-010	CD19	T cell	CRISPR	KO TRAC, PD1	Phase I
Cellectis	UCART22	CD22	T cell	TALEN	KO TRAC and CD52	Phase I/II
Cellectis	UCART20×22	CD20 and CD22	T cell	TALEN	KO TRAC and CD52	Phase I/II
Celyad	CYAD-211	BCMA	T cell	shRNA knockdown of TCR	CD3ζ	Phase I
Celyad	CYAD-101	NKG2D	T cell	TCR inhibitory molecule (TIM)	CD3ζ	Phase I
CRISPR Therapeutics	CTX112	CD19	T cell	CRISPR/Cas9	KO TRAC and B2M	Phase I
CRISPR Therapeutics	CTX131	CD70	T cell	CRISPR/Cas9	KO TRAC and B2M	Phase I
Fate Therapeutics	FT-819	CD19	iPSC-derived T cell	CRISPR/Cas9	KO TRAC	Phase I
Fate Therapeutics	FT522	CD19	iPSC-derived NK cell	CRISPR/Cas9	KO CD38	Phase I
Beam Therapeutics	Beam-201	CD7	T cell	Base editing	KO CD7, TRAC, CD52 and PD1	Phase I
BRL Medicine	BRL-301	CD19	T cell	CRISPR/Cas9	not disclosed	Phase I
Bioheng Therapeutics	CTD402	CD7	T cell	CRISPR/Cas9	KO CD7, TCR, etc.,	Phase I
Ucello Biotechnology	UC101	CD19	UCB-T cell	N/A	N/A	Phase I

Table 2. Several universal (allogeneic) cell therapy pipelines currently in clinical stages.

KACTUS’ Gene Editing Toolbox Accelerates the Development of Universal Cell Therapies

KACTUS is committed to providing high-quality genome editing tools for cell therapy companies. Backed by a certified quality management system and nearly 10,000 square meters of GMP manufacturing facilities, KACTUS has built a comprehensive product portfolio featuring a range of high-performing gene editing enzymes.

Among them, GMP-grade Cas9 protein has already been used by nearly 100 biopharmaceutical companies, supporting end-to-end needs from early research to clinical IND filings. In addition, AccuBase® Base Editor, a proprietary cytosine base editor developed by Base Therapeutics and licensed to KACTUS for GMP manufacturing and commercialization, has already advanced into the clinic with an IND application approved by the FDA.

Contact us to learn more about our gene editing enzymes or request a quote. For teams working on engineered TCR-T or CAR-T therapies, KACTUS also offers soluble TCR expression services to support TCR screening, validation, and downstream functional studies.