The study evaluates the safety and efficacy of CTX130, an allogeneic CD70-targeting chimeric antigen receptor (CAR) T-cell therapy, in patients with advanced or refractory clear cell renal cell carcinoma (ccRCC). CTX130 was developed using CRISPR-Cas9 gene editing to disrupt T-cell receptor (TCR) expression, β2-microglobulin (β2M), and CD70, enhancing T-cell function and reducing fratricide. Preclinical studies showed that CTX130 exhibited increased proliferation and cytotoxicity compared to unedited CAR T cells. In a phase I clinical trial (COBALT-RCC), 16 patients with relapsed/refractory ccRCC received CTX130 at various dose levels. No dose-limiting toxicities were observed, and disease control was achieved in 81.3% of patients. One patient achieved a durable complete response at 3 years. A next-generation CAR T construct, CTX131, which includes additional edits to enhance CAR T-cell expansion and potency, showed promising preclinical results. These findings provide proof of concept for CD70-targeted allogeneic CAR T-cell therapy in ccRCC and other CD70-expressing malignancies.The study evaluates the safety and efficacy of CTX130, an allogeneic CD70-targeting chimeric antigen receptor (CAR) T-cell therapy, in patients with advanced or refractory clear cell renal cell carcinoma (ccRCC). CTX130 was developed using CRISPR-Cas9 gene editing to disrupt T-cell receptor (TCR) expression, β2-microglobulin (β2M), and CD70, enhancing T-cell function and reducing fratricide. Preclinical studies showed that CTX130 exhibited increased proliferation and cytotoxicity compared to unedited CAR T cells. In a phase I clinical trial (COBALT-RCC), 16 patients with relapsed/refractory ccRCC received CTX130 at various dose levels. No dose-limiting toxicities were observed, and disease control was achieved in 81.3% of patients. One patient achieved a durable complete response at 3 years. A next-generation CAR T construct, CTX131, which includes additional edits to enhance CAR T-cell expansion and potency, showed promising preclinical results. These findings provide proof of concept for CD70-targeted allogeneic CAR T-cell therapy in ccRCC and other CD70-expressing malignancies.