A bispecific T cell engager recruits both type 1 NKT and Vγ9Vδ2-T cells for the treatment of CD1d-expressing hematological malignancies.

Bispecific T cell engagers (bsTCEs) hold great promise for cancer treatment but face challenges due to the induction of cytokine release syndrome (CRS), on-target off-tumor toxicity, and the engagement of immunosuppressive regulatory T cells that limit efficacy. The development of Vγ9Vδ2-T cell engagers may overcome these challenges by combining high therapeutic efficacy with limited toxicity. By linking a CD1d-specific single-domain antibody (VHH) to a Vδ2-TCR-specific VHH, we create a bsTCE with trispecific properties, which engages not only Vγ9Vδ2-T cells but also type 1 NKT cells to CD1d tumors and triggers robust proinflammatory cytokine production, effector cell expansion, and target cell lysis in vitro.

Gamma Delta T-Cell Based Cancer Immunotherapy: Past-Present-Future.

γδ T-cells directly recognize and kill transformed cells independently of HLA-antigen presentation, which makes them a highly promising effector cell compartment for cancer immunotherapy. Novel γδ T-cell-based immunotherapies, primarily focusing on the two major γδ T-cell subtypes that infiltrate tumors ( Vδ1 and Vδ2), are being developed. The Vδ1 T-cell subset is enriched in tissues and contains both effector T-cells as well as regulatory T-cells with tumor-promoting potential.

Marizomib alone or in combination with bevacizumab in patients with recurrent glioblastoma: Phase I/II clinical trial data.

Background: This phase I/II trial in patients with recurrent glioblastoma (GBM) evaluates the safety and preliminary efficacy of marizomib, an irreversible pan-proteasome inhibitor that crosses the blood-brain barrier.

Methods: Part A assessed the safety and efficacy of marizomib monotherapy. In Part B, escalating doses of marizomib (0.

Lenalidomide Maintenance After Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: A Meta-Analysis.

Purpose Lenalidomide maintenance therapy after autologous stem-cell transplantation (ASCT) demonstrated prolonged progression-free survival (PFS) versus placebo or observation in several randomized controlled trials (RCTs) of patients with newly diagnosed multiple myeloma (NDMM). All studies had PFS as the primary end point, and none were powered for overall survival (OS) as a primary end point. Thus, a meta-analysis was conducted to better understand the impact of lenalidomide maintenance in this setting.