title: Tumor ablation by intratumoral Ra-224-loaded wires induces anti-tumor immunity against experimental metastatic tumors.
abstract: BACKGROUND
  The current systemic anti-metastatic treatment is chemotherapy. Chemotherapy reacts mostly against replicating cells, which makes this therapy not specific. Moreover, resting cancer cells will not be destroyed. A better alternative is an engagement of the host immune system to react against tumor-associated antigens. An efficient immune-stimulating technique is an ablation of the tumor that results in the release of tumor antigens. Our ablation strategy is an innovative alpha-radiation-based technology, diffusing alpha-emitters radiation therapy (DaRT), which efficiently destroys local tumors and provides thereby an antigenic supply for antigen-presenting cells to stimulate T cells.
  
  
  METHODS
  Mice bearing weakly immunogenic DA3 adenocarcinoma or highly immunogenic CT26 colon carcinoma were treated by DaRT. Anti-tumor immune responses following tumor destruction were evaluated by (1) the resistance to a tumor challenge; (2) scanning by a CT imaging device for elimination of lung metastases; (3) improved tumor control when combining DaRT with an immunoadjuvant (CpG).
  
  
  RESULTS
  CT26 model: 63-77 % of DaRT-treated mice became resistant to a re-inoculated tumor compared to 29-33 % resistant mice in the control. DA3 model: (1) The growth rate of challenge tumors was the lowest in mice which their primary tumor was treated by DaRT. (2) Most (93 %) mice in the control group developed lung metastases compared to 56 % in the DaRT group. (3) Combining DaRT with CpG resulted in a better control of the primary tumor. Our study offers a technique to eliminate local and distant malignant cells, regardless of their replication status, by stimulating specific anti-tumor immunity through the supply of tumor antigens from the destroyed tumor.
authors.affiliation: Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, P.O. Box 39040, Tel Aviv, Israel.
authors.forename: Hila
authors.initials: H
authors.lastname: Confino
authors.forename: Ilan
authors.initials: I
authors.lastname: Hochman
authors.forename: Margalit
authors.initials: M
authors.lastname: Efrati
authors.forename: Michael
authors.initials: M
authors.lastname: Schmidt
authors.forename: Viktor
authors.initials: V
authors.lastname: Umansky
authors.forename: Itzhak
authors.initials: I
authors.lastname: Kelson
authors.forename: Yona
authors.initials: Y
authors.lastname: Keisari
mesh_terms: D055011:Ablation Techniques; D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000512:Alpha Particles / Q000627:therapeutic use*; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy*; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage; D047368:Tumor Burden / Q000528:radiation effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D009838:Oligodeoxyribonucleotides