title: Neoadjuvant therapy with interleukin-12-loaded polylactic acid microspheres reduces local recurrence and distant metastases.
abstract: BACKGROUND
  We previously demonstrated that the intratumoral injection of biodegradable polylactic acid microspheres that were loaded with interleukin (IL)-12 can induce a systemic antitumor immunity. We sought to investigate the clinical potential as neoadjuvant therapy.
  
  
  METHODS
  Mice were inoculated with 5 x 10(7) Line-1 cells subcutaneously. Six days later, a single intratumoral injection of IL-12- or BSA-loaded microspheres were given; 14 days later, autopsy was performed to document metastases. Mice were inoculated with 5 x 10(7) Line-1 cells and 10 days later either treated with IL-12- or BSA-loaded microspheres or resected. Treated tumors were resected 6 days after treatment. Mice were observed 45 days for local recurrence before autopsy.
  
  
  RESULTS
  Intratumoral injection of IL-12 microspheres resulted in significant suppression of tumor growth compared with controls (599 +/- 255 mm(3) vs 1591 +/- 372 mm(3); P =.001) and pulmonary metastases (0.4 vs 3.8 nodules per mouse; P =.003). Given before the operation, IL-12-loaded microspheres both decreased the local recurrence rate (100% to 40%) and pulmonary metastases (5.2 vs 0.6 nodules per mouse; P =.06). Earlier resection did not improve local recurrence or distant metastases.
  
  
  CONCLUSIONS
  Intratumoral injection of IL-12-loaded polylactic acid microspheres promotes the development of systemic antitumor immunity that can eradicate micrometastases. As a neoadjuvant therapy, this can result in decreased local and distant recurrence.
authors.affiliation: Division of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Sabel
authors.forename: H
authors.initials: H
authors.lastname: Hill
authors.forename: Y S
authors.initials: YS
authors.lastname: Jong
authors.forename: E
authors.initials: E
authors.lastname: Mathiowitz
authors.forename: R B
authors.initials: RB
authors.lastname: Bankert
authors.forename: N K
authors.initials: NK
authors.lastname: Egilmez
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D007109:Immunity / Q000187:drug effects; D015552:Injections, Intralesional; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000627:therapeutic use; D019344:Lactic Acid; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D011091:Polyesters; D011108:Polymers; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000276:Adjuvants, Immunologic; D011091:Polyesters; D011108:Polymers; D018664:Interleukin-12; D019344:Lactic Acid; C033616:poly(lactide)