Diffusing Alpha – emitters Radiation Therapy (DaRT) is based on intratumoral insertion of radioactive wires loaded with radium–224 releasing by recoil short–lived alpha–emitting atoms into the tumor that disperse to a considerable distance and lead to high dose alpha radiation region. DaRT Tumor cell disintegration following alpha radiation may serve as a supply of tumor antigens that will lead to the development of anti – tumor immunity.
Aims: 1. To test if DaRT mediated killing of tumor cells leads to the stimulation of anti-tumor immunity; 2. To examine the effect of T cells inhibition in combination with DaRT therapy; 3. To combine DaRT ablation approach with either immune stimulating or immune suppressor cell eliminating agents.
Methods: 1. Mice bearing DA3 breast carcinoma tumors were treated with Ra-224 loaded wires and mice resistance to re-inoculated tumor cells was measured. 2. The destruction of lung metastases was determined by CT scans. 3. Mice were treated with DaRT and Cyclosporine A simultaneously in order to inhibit T cells. 4. The immune-adjuvant, CpG or the T regulatory cell inhibitor, Cyclophosphamide (CP) at low dose, were used in combination with DaRT treatment.
Results: 1. Primary treated tumors or re-inoculated tumors in the DaRT - treated group were smaller compared to control groups. 2. Forty nine days post treatment only 71% of the DaRT – treated mice had lung metastases, compared to 100% in the inert group. 3. T cell inhibition did not affect primary tumor development. 4. The combined treatment of DaRT with either CpG or CP augmented the ablation of the primary tumor and survival. Most (60%) of the DaRT and CpG treated mice survived 82 days post treatment compared to 20-40% survival in the control groups. The combined treatment of DaRT and CP prolonged mice survival. In the DaRT and CP treated group, 83% survived compared to 0-33% survival in the control groups, 104 days post treatment.
Conclusions: Taken together, these results indicate that alpha radiation based therapy inhibits tumor development and metastatic load. The destruction of the tumor stimulated a systemic anti tumor immunity, which was augmented when combined with immune adjuvants or anti -immune suppressor cells agents.
