The 2025 State of Allogeneic Cell Therapies in Oncology
Allogeneic Cancer Cell Therapies: Shifting Paradigms in Treatment Efficacy and Safety
Allogeneic cancer cell therapies promise to eliminate major drawbacks of autologous CAR-T cells, namely slow and often unsuccessful cell manufacturing, inconsistent potency, and a very high price tag. A lower price can indeed be achieved by allogeneic cells given the lack of manufacturing and scaled-up production. The advantage of fast administration should not be underestimated – a large percentage of patients with relapsed blood cancers require a different (bridging) treatment while waiting for CAR-T cells to be manufactured, and unfortunately, many progress rapidly and die before they can be infused. For instance, in a multiple myeloma study, only 89 out of 185 patients waitlisted to receive J&J’s Carvykti (ciltacabtagene autoleucel) or BMS’/2seventy bio’s Abecma (idecabtagene vicleucel) ended up receiving an infusion [1].
By the time the first autologous CAR-T cell product received FDA approval (Novartis’ Kymriah (tisagenlecleucel for R/R B-ALL, in August 2017 [2]), Cellectis’ UCART19, the first allogeneic CAR-Ts had entered clinical trials [3]. While UCART19 did not succeed in the clinic, many other companies moved forward with allogeneic programs, with major players including Allogene Therapeutics, Fate Therapeutics, Caribou Biosciences, and Nkarta, among others.
Between 2017 and 2024, numerous clinical trials emerged, yet the robust, large-scale efficacy data investors anticipated remained elusive. While many programs reported promising safety and efficacy, results were consistently limited to small patient cohorts. By 2024, after early signs of success in autoimmune disorders, several companies shifted their focus from oncology to autoimmune applications. The only success came from assets adjunctive to stem cell transplants, such as Ebvallo (tabelecleucel) which received EMA approval for patients with relapsed or refractory Epstein Barr virus-positive post-transplant lymphoproliferative disease in 2022.
A notable strategic pivot came in 2023. Allogene ($ALLO) famously changed its strategy by announcing the ALPHA3 1L large B-cell lymphoma (LBCL) study for its allo-CAR-T cemacabtagene ansegedleucel, marking a strategic expansion to include first-line treatment, which however ended up becoming the company’s flagship setting, replacing the ALPHA2 study for R/R LBCL. This is a high-risk, high-reward move since the use of cell therapies in consolidation is not proven, but if successful would unlock a large patient pool.
In 2025, Allogene disclosed a new dataset (n=33) from the ALPHA2 study which provided more evidence of activity and safety for cema-cel. The overall response rate was 58% and the complete response (CR) rate was 42%. Most impressively, no cases of graft-versus-host disease (GvHD), neurotoxicity syndrome, or grade ≥3 cytokine release syndrome were reported. Unfortunately, the study did not disclose the duration of response (DoR) in all patients, only in patients who achieved a CR (23.1 months) [4]. This dataset suggests that, at least from a safety standpoint, allogeneic CAR‑T therapies can match—or even exceed—the profile of autologous products, effectively dispelling long‑standing investor concerns over GvHD. However, while the response rate seems to be comparable with auto-CAR-Ts in the same setting, the absence of DoR data leaves the question of durability unanswered yet again. With Allogene focusing on the 1L setting, other companies will have to provide robust data.
As of February 2025, key programs in this area are:
- Allogene’s cema-cel (1L LBCL, Phase II pivotal)
- CRISPR Therapeutics’ CTX112 (R/R NHL, Phase I)
- Fate’s FT522 (R/R NHL, Phase I)
- Cellectis’ UCART22 (R/R ALL, Phase I)
- Caribou’s CB-010 (R/R NHL, Phase I)
- Nkarta’s NKX019 (R/R NHL, Phase I)
By Sakis Paliouras, PhD
References
[1] ASH 2024 Abstract: Real-world study on CAR-T cell therapy waiting times and outcomes in multiple myeloma patients
[2] FDA approval announcement for Kymriah (tisagenlecleucel) for B-cell ALL and tocilizumab for cytokine release syndrome
[3] Cellectis press release: First patient treated with UCART19 in pediatric acute B-lymphoblastic leukemia trial
[4] Allogene Therapeutics announces publication of durable response data from ALPHA2 study of cema-cel
