Cell death inducing external beam radiation (EBRT) combined with experimental intratumoral injection of dendritic cells (DC) showed promise by initiating anti-autologous tumor-cell immune responses in mice. Here we performed first clinical trial testing this hypothesis in patients with large high-grade soft tissue sarcomas (STS). This type of cancer has a significant (>50%) risk of progressing to distant metastases. Patients with clinical stage T2N0M0 or T3N0M0 high-grade STS of the extremity/trunk/chest wall were treated with standard neo-adjuvant EBRT 5040 cGy / 180 cGy coordinated with experimental DC therapy consisting of DC progenitor apheresis, ex-vivo expansion and culture, and 4 × intratumoral injections of 10 million DC. Autologous DC product was performed according to standardized GMP laboratory procedures. T cell function was assessed by EliSpot (measuring IFN-γ production) and proliferation (thymidine uptake) in addition to phenotyping of peripheral blood mononuclear cells by flow cytometry.

Clinically, targeted accrual was reached with eighteen patients completing neo-adjuvant EBRT with experimental intratumoral DC therapy. All patients have completed full immunologic assessment. Ten patients (56%) were induced to produce significant immune responses against autologous tumor cell lysates or/and survivin antigens as determined using ELISPOT assays or cell proliferation. Interestingly, some of these responses persisted even 30 weeks after start of treatment. Extensive post treatment T cell infiltration was detected within tumors. No clinical toxicity has been observed. Suggestive clinical outcome on 14 patients followed 1 year reveal progress in 1/7 patients with robust response (detected at more than one time point), and 4/7 patients with weak (detected at one time point at the beginning of the study) or no response respectively. Thus, this data is promising for planning future combined treatment approaches as radiation therapy/immunotherapy.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2411.