second generation 4-1BBζ B7H3-EGFRt-DHFR + second generation 4-1BBζ CD19-Her2tG

This is a combination autologous CAR-T cell therapy composed of two distinct engineered T cell products. The first component, "second generation 4-1BBζ B7H3-EGFRt-DHFR," consists of autologous CD4+ and CD8+ T cells lentivirally transduced to express a chimeric antigen receptor (CAR) targeting the tumor-associated antigen B7-H3 (CD276), with a co-stimulatory domain from 4-1BB (CD137), an EGFR truncated safety/suicide switch (EGFRt), and dihydrofolate reductase (DHFR) for selection or tracking. The second component, "second generation 4-1BBζ CD19-Her2tG," comprises autologous T cells expressing a CAR targeting the B-cell marker CD19, also with a 4-1BB co-stimulatory domain and Her2 truncated gene tag (Her2tG) as an additional safety or tracking feature. This dual-targeted approach aims to enhance anti-tumor efficacy by simultaneously attacking solid tumors expressing B7-H3 and leveraging the presence of normal or malignant CD19+ cells to promote CAR-T expansion and persistence. Both constructs include suicide switches that allow selective elimination of infused CAR-T cells in case of severe toxicity using clinically available monoclonal antibodies against EGFR or HER2[2][6][4]. Primary indications are relapsed/refractory non-CNS solid tumors in pediatric and young adult patients.