Engineered CAR-T cells reduce Alzheimer’s plaques in mouse study

The first use of CAR-T cells for a neurodegenerative disease has shown that engineered immune cells can reduce Alzheimer’s-associated plaques in mice. The team, led by scientists at the Weizmann Institute of Science and Washington University School of Medicine, isolated T cells from healthy mice and engineered them to recognize amyloid proteins in the brain. When injected into mice with established amyloid-beta plaques, the CAR-T cells led to a significant reduction in amyloid deposits and lowered markers of brain-tissue inflammation. Future studies will explore whether the approach can be used not only to clear pathological proteins, but also to deliver therapeutic agents and support tissue repair in the brain. Source

Stem cell memory CAR-T cells achieve remissions at low doses

A first-in-human study suggests that stem cell memory CAR-T cells could offer a more potent and predictable platform for next-generation cell therapies. In patients with relapsed or refractory CD19+ B-cell malignancies after allogeneic stem cell transplant, a highly defined CD8+ CAR-T product enriched for stem cell memory T cells achieved complete responses at very low doses – and without the lymphodepleting chemotherapy normally used before CAR-T infusion.

The approach is designed to address a key limitation of current CAR-T products: variability in expansion, persistence, and toxicity. Compared with conventional CAR-T cells, the stem cell memory product showed stronger expansion and longer persistence in patients, while maintaining a reservoir of self-renewing, stem-like cells that could support durable immune activity over time. Notably, the therapy appeared to separate CAR-T expansion from severe toxicity. Even when CAR-T levels reached ranges associated with serious cytokine release syndrome in standard CAR-T studies, patients receiving the stem cell memory product experienced only mild side effects. Source 

Dual-targeting CAR-T shows complete responses in myeloma and POEMS syndrome

Tempest Therapeutics has reported updated Phase 1 data for TPST-2003, its autologous dual-targeting CD19/BCMA CAR-T therapy, showing complete responses across all CAR-T-naïve efficacy-evaluable patients treated in two ongoing studies. Across REDEEM-1 in relapsed/refractory multiple myeloma and POEMS-1 in POEMS syndrome, 15 of 15 evaluable CAR-T-naïve patients achieved complete response measures, including 10 multiple myeloma patients by IMWG criteria and five POEMS patients by normalization of VEGF levels.

TPST-2003 is designed to target both CD19 and BCMA in parallel, aiming to address tumor heterogeneity and antigen escape – two barriers to durable responses in plasma cell disorders. Across REDEEM-1 and a prior investigator-initiated study, all 29 CAR-T-naïve evaluable patients with measurable disease at baseline responded, including 18 patients with extramedullary disease, a high-risk group that often responds poorly to standard therapies.

The safety profile reported to date appears favorable, with no Grade 3 or higher cytokine release syndrome or ICANS in REDEEM-1, and no dose-limiting toxicities reported in POEMS-1. The company says the results support plans to discuss a potential US registrational study with the FDA later this year. Source

OpRegen cell therapy shows durable vision gains in geographic atrophy

Lineage Cell Therapeutics has reported 36-month results from a Phase 1/2a study of OpRegen, an allogeneic retinal pigment epithelial cell therapy for geographic atrophy (GA) secondary to age-related macular degeneration. Among Cohort 4 patients completing three-year follow-up, treated eyes showed a mean gain of +6.2 ETDRS letters, with stronger gains of +9.0 letters in the five patients whose atrophic lesions received extensive OpRegen coverage during subretinal delivery.

The therapy is designed to replace or support damaged retinal pigment epithelial cells, which are lost in GA and contribute to progressive vision loss. OCT imaging suggested sustained structural improvements, including partial restoration of outer retinal layers, reappearance of an RPE layer, and features associated with photoreceptor recovery. Treated eyes also showed maintained improvements in RPE-complex and external limiting membrane areas, while untreated fellow eyes continued to decline over the same period. The therapy is now being evaluated in the Phase 2a GAlette study, which is focused on optimizing subretinal delivery to target areas of atrophy. Source

Optogenetic gene therapy restores light perception in early RP trial

Restore Vision has reported interim first-in-human data for RV-001, a GPCR-based optogenetic gene therapy for advanced retinitis pigmentosa (RP). In the ongoing Phase 1/2 trial in Japan, six patients with no light perception received a single intravitreal injection across low- and high-dose cohorts, with no dose-limiting toxicities or drug-related serious adverse events reported to date.

RV-001 uses an AAV vector to deliver a chimeric rhodopsin designed to restore light sensitivity through native G-protein-mediated phototransduction. Unlike some optogenetic approaches, the therapy is being developed to work under natural ambient light conditions without goggles or external devices, and could be applicable across RP patients regardless of the underlying genetic mutation.

Early efficacy signals appeared dose dependent. In the high-dose cohort, all three patients improved from no light perception to light perception or better within one month, with one patient achieving chart-based visual acuity measurable by the Berkeley Rudimentary Vision Test. Improvements were also supported by full-field stimulus testing and functional assessments, including mobility and object recognition tasks. Source

Europe’s first CAR-T trial for AL amyloidosis opens

UCL and UCLH researchers have launched Europe’s first clinical trial testing CAR-T cell therapy in patients with light chain amyloidosis (AL), a rare and serious blood disorder with limited options for those who relapse or fail to respond to chemotherapy. Three patients have already been treated in the Phase 1 ALARIC trial, which aims to enroll at least 12 patients at UCLH over the next two years, with a second site expected to open in Leeds.

AL amyloidosis occurs when abnormal plasma cells produce misfolded light-chain proteins that build up in organs and tissues, potentially leading to organ failure. The investigational CAR-T approach is designed to target BCMA and CD19 on disease-driving plasma cells, building on the success of BCMA-directed CAR-T therapies in multiple myeloma.

The trial’s first priority is safety, but investigators hope the one-off therapy could deliver deep, durable responses while reducing the burden of prolonged chemotherapy and maintenance treatment. One early participant reported that his lambda light-chain levels became “almost immeasurable” after infusion. Source

Cabaletta raises $150 million to advance autoimmune CAR-T pipeline

Cabaletta Bio has priced a $150 million underwritten offering to support development of its targeted cell therapy pipeline for autoimmune diseases. The financing includes participation from existing and new investors, as well as Eli Lilly and Company, and comes as Cabaletta advances rese-cel, its investigational fully human CD19 CAR-T therapy, across multiple autoimmune indications.

Rese-cel is being evaluated in the company’s RESET clinical development program, which spans lupus, myositis, systemic sclerosis, myasthenia gravis, and pemphigus vulgaris. The therapy is designed to deplete CD19-expressing B cells and potentially reset immune tolerance, with the aim of delivering deep and durable responses in diseases driven by pathogenic autoimmunity. The offering follows Cabaletta’s recent manufacturing partnership with Cellares to support potential large-scale production of rese-cel. Source

Epicrispr and Forge partner to scale AAV manufacturing for FSHD gene therapy

Epicrispr Biotechnologies and Forge Biologics have announced a strategic manufacturing partnership to support EPI-321, Epicrispr’s investigational AAV gene-modulating therapy for facioscapulohumeral muscular dystrophy (FSHD). Forge is providing AAV process development, cGMP manufacturing, and analytical development services, with clinical material now being used in a first-in-human trial across the US, New Zealand, and Australia. Source

Johnson & Johnson discontinues lymphoma CAR-T programs

Johnson & Johnson has discontinued two investigational CAR-T programs for large B-cell lymphoma: a CD20 mono CAR-T therapy and a CD19-CD20 bi-CAR-T therapy. The company described the move as a strategic business decision based on portfolio priorities and the changing treatment landscape in large B-cell lymphoma. Source