Neoadjuvant therapy with interleukin-12-loaded polylactic acid microspheres reduces local recurrence and distant metastases

• Published in: Surgery Vol. 130; no. 3; pp. 470 - 478
• Main Authors: Sabel, Michael S., Hill, Hank, Jong, Yong S., Mathiowitz, Edith, Bankert, Richard B., Egilmez, Nejat K.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01-09-2001; Elsevier
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - immunology; Adenocarcinoma - prevention & control; Adenocarcinoma - secondary; Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - therapeutic use; Animals; Antineoplastic agents; Biological and medical sciences; Chemotherapy; Immunity - drug effects; Injections, Intralesional; Interleukin-12 - administration & dosage; Interleukin-12 - therapeutic use; Lactic Acid; Medical sciences; Mice; Mice, Inbred BALB C; Microspheres; Neoadjuvant Therapy; Neoplasm Recurrence, Local - prevention & control; Pharmacology. Drug treatments; Polyesters; Polymers; Skin Neoplasms - drug therapy; Skin Neoplasms - immunology; Tumor Cells, Cultured; Animal model; Load; Relapse; Microsphere; Lactic acid copolymer; Cytokine; Rodentia; Interleukin 12; Intratumoral administration; Metastasis; Malignant tumor; Neoadjuvant treatment; Prevention; Vertebrata; Chemotherapy; Mammalia; Mouse; Animal
• ISSN: 0039-6060; 1532-7361
• DOI: 10.1067/msy.2001.115839

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.
Mice were inoculated with 5 × 107 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 × 107 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.
Intratumoral injection of IL-12 microspheres resulted in significant suppression of tumor growth compared with controls (599 ± 255 mm3 vs 1591 ± 372 mm3; 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.
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.