Related Experiment Video
Updated: Jul 16, 2026
In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function
Published on: February 27, 2019
Allogeneic CD70-Targeted Chimeric Antigen Receptor T-Cell Therapy for Advanced Renal Cell Carcinoma: Results From the
Samer A Srour1, Jad Chahoud2, Alexandra Drakaki3
1Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
Purpose:
Treatment options for clear cell renal cell carcinoma (ccRCC) refractory to immune checkpoint inhibitors (ICIs) and targeted therapy are needed. ALLO-316 is an allogeneic chimeric antigen receptor (CAR) T-cell product that targets CD70-expressing ccRCC and resists immune rejection by targeting and eliminating patients' CD70+ alloreactive T cells.
Methods:
In the phase Ia/b TRAVERSE trial (ClinicalTrials.gov identifier: NCT04696731), patients with advanced ccRCC resistant to ICIs and vascular endothelial growth factor receptor-targeted therapy received lymphodepletion and ALLO-316 following a modified 3 + 3 design. Phase Ia evaluated ALLO-316 dose and fludarabine/cyclophosphamide (FC)-based lymphodepletion with/without the anti-CD52 antibody, ALLO-647. Additional patients were enrolled in phase Ib to confirm the expansion regimen identified in phase Ia. Primary end points were dose-limiting toxicities (DLTs) and adverse events (AEs).
Results:
Fifty-one patients were enrolled (phase Ib, n = 23). Patients received a median of four prior lines of therapy. The median follow-up was 28.8 months. DLTs occurred in two patients who received ALLO-647 (grade 3 autoimmune hepatitis; grade 5 cardiogenic shock). Grade ≥3 cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome occurred in 2.0%, 0%, and 6.0% of patients, respectively. Most grade ≥3 AEs were hematologic (neutropenia 62.0%; white blood cell count decreased 54.0%; anemia 36.0%). In phase Ib, patients received FC and 80 × 106 CAR T cells. The objective response rate was 17.4% overall, 25.0% in phase Ib patients and 31.3% in phase Ib patients with CD70 tumor proportion score ≥50%.
Conclusion:
ALLO-316 had manageable safety and encouraging antitumor activity in CD70-positive ccRCC. The TRAVERSE trial demonstrates proof of concept for the role of allogeneic CAR T-cell therapy in solid tumors.
