Patients with T-cell acute lymphoblastic leukaemia (T-ALL) and the closely related peripheral T-cell lymphoblastic lymphoma (PTCL) represent a group with a notable absence of targeted therapy options. Current treatments depend entirely on combination chemotherapy, after which approximately 60% of first-line patients progress to refractory or relapsed (R/R) disease and are in need of stem cell transplantation (HCT). While chimeric antigen receptor T-cell (CAR-T) therapy has transformed B-cell acute lymphoblastic leukaemia (B-ALL), this has not extended to T-cell lymphoma/leukaemia. A major reason is the occurrence of fratricide-antigen targets presented on malignant T-cells are also expressed on the surface of therapeutic CAR-T cells, resulting in the self-elimination of the therapeutic cells.
At the American Society for Clinical Oncology (ASCO) Annual Meeting, held May 29–June 2, 2026, researchers at Peking University People’s Hospital presented Phase I results from its CONQUER trial (NCT06874946). This evaluated a novel, nanobody-based autologous CD5 CAR-T therapy for T-ALL/PTCL and cutaneous TCL. CD5 is a pan–T-cell marker that downregulates T-cell activation and is highly expressed on malignant cells. The presented CAR-T construct, SL105, uses endogenous production of nanobodies within the CAR-T cells to block CD5 before it is expressed on the CAR-T cell’s surface, meaning CD5 nanobodies expressed on the surface will only recognize target cells, eliminating the risk of fratricide.
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22 adult R/R patients were infused with a single dose of SL105 at 0.5, 1.0, or 2.0 ×106 CAR-T cells/kg (at least five patients per level). The median time to peak CAR-T expansion was 14 days, with the median level reaching 6.3 ×104 copies/μg. No dose-limiting toxicities were observed within the first 28 days, and CAR-T persistence up to six months was observed in one patient. Cytokine release syndrome (CRS) was observed in 72.7% of patients, but exclusively Grade 1 (50%) or Grade 2 (21.7%), and with manageable haematotoxicity. Initial efficacy was favourable, with a three-month maximum objective response rate (ORR) of 81.8%, combined complete response (CRc) of 54.5%, and all responding patients were confirmed as minimal residual disease (MRD)-negative by flow cytometry. However, overall, there was a striking incidence of infection. 90.9% of patients encountered infections of Grade 3 or higher, with 63.6% encountering Epstein-Barr virus (EBV) and 45.5% cytomegalovirus (CMV) infections. Seven infection-related deaths occurred in patients who had not progressed to consolidative HCT, and the overall survival reported within the trial was a median 3.6 months. It is important to note that an undisclosed number of patients refused allogeneic HCT, and outcomes were not stratified by patient subgroup or prior treatment, which may skew negative interpretations of the data. Further work is in place to apply the recommended Phase II dose (RP2D) of 2.0 x106 CAR-T cells/kg in a necessarily larger cohort and to introduce protocol modifications to ensure HCT is provided earlier after CAR-T administration, with the aim of reducing the incidence of non-relapse mortality.
This is the second publication of a non-gene edited autologous CD5 CAR-T therapy for R/R T-ALL to be presented in the last seven months. In November 2025, US-based March Biosciences released interim results from its Phase II trial of its construct, MB-105 (NCT06534060), a follow up from its positive 2023 trial (NCT0308190). This study was smaller, with only four patients evaluated after 28 days; however, ORR was 100%, with most adverse events at Grade 1, and CRS in 50% of patients. Again, two cases of viral reactivation or infection were observed, however, these were reported as Grade 2 or lower. GlobalData’s likelihood of approval (LoA) assessment currently projects MB-105 at a low 12%, for treatment of T-ALL. The positive short-term efficacy and safety profiles of these treatments may be promising for applying these therapies as a bridge to more curative allogeneic HCT options, but without modifications to lower the risk of infectious disease and improved long term survival, they are yet to be a revelation as independent therapies.
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