Neoadjuvant therapy with interleukin-12-loaded polylactic acid microspheres reduces local recurrence and distant metastases.
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.
Sabel
M S
MS
Division of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Hill
H
H
Jong
Y S
YS
Mathiowitz
E
E
Bankert
R B
RB
Egilmez
N K
NK
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
D000276:Adjuvants, Immunologic; D011091:Polyesters; D011108:Polymers; D018664:Interleukin-12; D019344:Lactic Acid; C033616:poly(lactide)