STAb-T therapy / University Hospital October 12, CNIO - LARVOL DELTA

Simultaneous secretion of a PD-L1 x 4-1BB bispecific antibody improves antileukemic efficacy of STAb-T cells secreting a CD19-specific T-cell engager. (PubMed, Oncoimmunology) - "Preclinical data show that this combination improves cytotoxic activity and prolongs antileukemic efficacy compared with low-dose single STAb-T therapy. Our findings suggest that the integration of PD-L1 × 4-1BB bsAbs into STAb-T19 therapy may maximize efficacy, thereby opening a promising avenue to address resistance and relapse in B-ALL. Moreover, this approach may pave the way for the development of next-generation cell-based therapies for hematologic and solid malignancies."

Journal • Hematological Disorders • Hematological Malignancies • Oncology • Solid Tumor

CD4+ tumor-infiltrating lymphocytes secreting T cell-engagers induce regression of autologous patient-derived non-small cell lung cancer xenografts. (PubMed, Oncoimmunology) - "A promising approach based on the production of bispecific T cell-engagers (TCE) by engineered T cells (STAb-T therapy) improves the efficacy of current T cell redirection strategies against tumor-associated antigens in hematological tumors...We confirmed that the standard TIL expansion protocol promotes the loss of tumor-dominant T cell clones and the overgrowth of virus-reactive TCR clonotypes that were marginally detectable in primary tumors. We demonstrated the antitumor activity of TILSTAb both in vitro and in vivo when administered intratumorally and systemically in an autologous immune-humanized PDX EGFR+ NSCLC mouse model, where tumor regression was mediated by TCE-redirected CD4+ TIL bearing non-tumor dominant clonotypes."

Journal • Tumor-infiltrating lymphocyte • Hematological Disorders • Hematological Malignancies • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Transplantation • CD4 • EGFR • TRB

Spanish Researchers Developing Autologous ’STAb’ Therapy to Overcome CAR T-Cell Limitations (Precision Medicine Online) - "'STAb' stands for secretion of T-cell engager antibodies, and Luis Alvarez-Vallina, the head of CNIO's H12O-CNIO Cancer Immunotherapy Clinical Research Unit, is among the researchers pushing to move STAb T-cell therapy into clinical trials for patients with hematologic malignancies and solid tumors...According to Alvarez-Vallina, his team is in the final stages of securing regulatory clearance to begin a first-in-human trial of STAb T-cell therapy in Europe this summer. The researchers plan to enroll around 15 patients with CD19-positive lymphomas and other advanced hematologic malignancies...Additionally, he said that the recent preclinical study shows the STAb T-cell approach could have a unique advantage when it comes to treating B-cell maturation antigen (BCMA)-expressing multiple myeloma....Once his team secures European regulatory clearance, the forthcoming first-in-human clinical trial is expected to launch in multiple centers across Spain."

New trial • Preclinical • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology • Solid Tumor