Aug 2026· Cell and Gene Therapy Insights· Vol 12, pp. 723–728· 0 citations
Abstract
July 2026 saw the field push access outward on multiple fronts, from the first FDA approval of a genetic therapy for children as young as 2 years (Vertex’s CASGEVY) to the first international patient treated with satri‑cel, the first CAR‑T therapy approved anywhere for a solid tumor. Regulatory momentum extended across in vivo CAR‑T, allogeneic transplant, and solid tumor cell therapy, while ARPA‑H committed up to $160 million to scalable in vivo gene editing for rare diseases. Alongside these milestones, new partnerships, a €33 million financing, and first patient dosings in pivotal trials for Gaucher disease type 1 and diabetic retinopathy signaled continued investment across the manufacturing, clinical, and commercial landscape.
June delivered a landmark for the CAR-T field alongside a distinct shift in US regulatory posture. CARsgen secured NMPA approval for satri-cel, the first CAR-T cell therapy approved for a solid tumor indication anywhere in the world, targeting Claudin18.2 in advanced gastric and gastroesophageal junction adenocarcinoma. In parallel, the US FDA signaled a more accommodating stance on accelerated approval, a shift coinciding with recent changes in agency leadership, as uniQure reversed course on AMT-130 for Huntington’s disease and REGENXBIO cleared a path to resubmit NAVSUNLI for MPS II (Hunter syndrome).
Abigail Pinchbeck· Cell and Gene Therapy Insigh...· 0 citations
Adoptive cell therapies utilizing both gene-modified and unmodified immune cells have revolutionized treatments for cancer and infection. Seven Chimeric antigen receptor (CAR) T cell products have been approved as therapies, providing the momentum to expand their clinical benefit to several cancer types. Many novel receptor-expressing cell therapies remain in preclinical development and require robust clinical testing Translating these into early-phase clinical trials requires navigating manufacturing, quality, and regulatory systems that are often not documented explicitly for academic investigators. This manuscript provides a stage-by-stage roadmap for translating academic CAR T-cell research into an investigator-led Phase I clinical trial in the Australian public sector. It draws on the E2CAR program, the first clinical translation of an EphA2-directed CAR T-cell product into pediatric bone sarcoma, conducted at the Children’s Hospital at Westmead. We present our experience across six stages: construct finalization and vector strategy, manufacturing process development, quality infrastructure, assay development and validation, multi-entity operational coordination, and CTA regulatory engagement and provide recommendations for researchers at each stage. We also present a consolidated program timeline, minimum personnel requirements, and indicative costs to support grant applications and institutional planning. While the operational framework described here was developed specifically for our Health Precinct some of the recommendations we provide are likely to benefit academic groups navigating constraints in comparable settings.
Rui Tan, R. Walsh, G. McCowage et al.· Frontiers in Medicine· 0 citations
Chimeric antigen receptor (CAR)-T cell therapy has revolutionized hematological oncology, yet conventional ex vivo manufacturing imposes severe clinical and economic burdens. In vivo CAR-T therapy—programming endogenous T cells via systemic vector delivery—has emerged to overcome these limitations. This communication analyzes the 2026 inflection point in in vivo CAR-T development, comparing lentiviral versus mRNA-LNP platforms. Early candidates (ESO-T01, LB2501) show promising efficacy and reduced toxicities, but urgent challenges persist: variable transduction efficiency, vector immunogenicity, off-target risks, and regulatory harmonization. Resolving these hurdles is imperative to translate this paradigm-shifting modality into standard clinical practice.
M. Ni· BioNatura Journal: Ibero-Ame...· 0 citations
The approval of lifileucel in 2024 marked an important milestone in oncology as the first cellular therapy authorized for a solid tumor. This milestone stands in sharp contrast to the success of CAR-T cells in hematologic malignancies, where six products have been licensed, and highlights the central challenge that solid tumors remain largely unconquered. At the mechanistic core lies a three-stage framework describing the major barriers encountered by therapeutic T cells in solid tumors, a series of escalating barriers that any therapeutic T cell must overcome to achieve durable tumor control: (1) Access: overcoming stromal and vascular barriers that restrict T-cell infiltration into tumors, (2) Recognition: identifying malignant cells in the setting of antigen heterogeneity and immune evasion, and (3) Persistence: maintaining T-cell function within the immunosuppressive tumor microenvironment. Historically, CAR-T and TIL therapies were viewed in competition, each occupying distinct niches. The field is increasingly adopting a convergent paradigm in which both platforms address a common challenge: overcoming the biological barriers that limit durable responses in solid tumors through complementary engineering and biological strategies. We review the biological obstacles, emerging convergence strategies, and translational frameworks including biomarker-guided patient selection that define this new area. Therapeutic selection may increasingly be guided by a tumor’s dominant biological barriers rather than by platform classification alone.
Duc-Hiep Bach, Van T. Hoang, T. Pham et al.· Cancer Cell International· 1 citation
Background Chimeric antigen receptor (CAR) T-cell therapy in solid tumors is hindered by the immunosuppressive tumor microenvironment and by toxicities associated with viral-vector manufacturing. Non-viral gene delivery platforms have emerged as a potential alternative, though clinical evidence remains fragmented. Methods Following an a priori protocol registered on the Open Science Framework (OSF; https://doi.org/10.17605/OSF.IO/2TPQS) and adhering to JBI/PRISMA-ScR guidelines, a systematic search was conducted across four databases from inception through May 15, 2026. Patient-level data were extracted to describe cellular persistence and clinical outcomes across strictly non-viral delivery platforms. Results Four early-phase studies met the inclusion criteria, encompassing 28 heavily pretreated patients with metastatic solid tumors. Two non-viral platforms were identified: mRNA electroporation (n=19; intravenous in 13, intratumoral in 6) and the piggyBac transposon system (n=9). Across both mRNA routes, transient CAR-T persistence (<7 days) was observed, with no objective responses (ORR 0%), though disease stabilization yielded a disease control rate (DCR) of 53%; cross-route comparison is limited by differing distribution profiles. The piggyBac system showed longer persistence (~28 days) and a DCR of 78%, including the only documented objective response (ORR 11%). No Grade ≥3 cytokine release syndrome or neurotoxicity was reported in any of the 28 patients, and no tocilizumab or systemic corticosteroids were required. Conclusions Within this limited early-phase evidence base, no severe toxicities attributable to non-viral platforms were reported, and the evidence identifies knowledge gaps warranting prospective investigation. mRNA platforms showed transient persistence and disease stabilization in 53% of patients. One partial response was documented with the piggyBac platform in a single patient; however, this outcome cannot be attributed to the delivery platform given simultaneous differences in target antigen, tumor histology, route of administration, and geographic setting. No firm conclusions regarding comparative platform performance can be drawn from this evidence base. Systematic review registration https://doi.org/10.17605/OSF.IO/2TPQS, identifier OSF.IO/2TPQS.
Favio Varón Suárez, J. Moreno, Oriana Arias-Valderrama et al.· Frontiers in Immunology· 0 citations
Nearly 11 years after T-VEC became the first oncolytic virus approved in a major market, the closest candidate to follow it-Replimune's RP1, now facing an FDA advisory committee-remains a locally injected herpesvirus for melanoma, underscoring how little the field has advanced. Researchers blame a stack of unresolved obstacles-flawed trial designs, mistimed drug combinations, tumor defenses, such as hypoxia, and the inability to deliver most viruses intravenously-even as smarter sequencing, neoadjuvant approaches, and a bladder-cancer virus near approval hint at renewed momentum.
Unknown authors· Cancer Discovery· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
