Journal article
A therapeutic microparticle-based tumor lysate vaccine reduces spontaneous metastases in murine breast cancer
The AAPS journal, Vol.16(6), pp.1194-1203
11/2014
DOI: 10.1208/s12248-014-9662-z
PMCID: PMC4389752
PMID: 25224145
Abstract
Metastatic breast cancer is currently incurable, and available therapies are associated with severe toxicities. Induction of protective anti-tumor immunity is a promising therapeutic approach for disseminated breast cancer, as immune responses are (i) systemic; (ii) antigen-specific; and (iii) capable of generating long-lived "memory" populations that protect against future tumor recurrences. Pursuant with this approach, we have developed a novel heterologous prime/boost vaccination regimen that reduces spontaneous lung metastases in mice with established murine 4T1 adenocarcinoma breast tumors. In our studies, mice were orthotopically challenged with luciferase-expressing 4T1 tumor cells; luciferase expression was retained in vivo, enabling us to quantitatively track metastatic tumor growth via bioluminescent imaging. On day 6 post-challenge, mice received a therapeutic "prime" consisting of bulk tumor lysates encapsulated in poly(lactic-co-glycolic) acid (PLGA) microparticles (MPs). On day 11, mice received a "boost" composed of free tumor lysates plus a cocktail of Toll-like receptor (TLR)-stimulating adjuvants. Tumor progression was monitored in vaccinated and untreated mice for 25 days, a time at which 100% of untreated mice had detectable lung tumors. PLGA MPs injected subcutaneously trafficked to draining lymph nodes and were efficiently phagocytosed by dendritic cells (DCs) within 48 h. Our combination therapy reduced metastatic lung tumor burdens by 42% and did not induce autoimmunity. These findings illustrate that vaccines based upon MP delivery of tumor lysates can form the basis of an effective treatment for metastatic breast cancer and suggest that similar approaches may be both efficacious and well-tolerated in the clinic.
Details
- Title: Subtitle
- A therapeutic microparticle-based tumor lysate vaccine reduces spontaneous metastases in murine breast cancer
- Creators
- Brett P Gross - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, 52242, USAAmaraporn WongrakpanichMeghan B FrancisAliasger K SalemLyse A Norian
- Resource Type
- Journal article
- Publication Details
- The AAPS journal, Vol.16(6), pp.1194-1203
- DOI
- 10.1208/s12248-014-9662-z
- PMID
- 25224145
- PMCID
- PMC4389752
- NLM abbreviation
- AAPS J
- ISSN
- 1550-7416
- eISSN
- 1550-7416
- Publisher
- United States
- Grant note
- P30 ES005605 / NIEHS NIH HHS P30CA086862 / NCI NIH HHS P30 CA086862 / NCI NIH HHS R01 CA181088 / NCI NIH HHS
- Language
- English
- Date published
- 11/2014
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering
- Record Identifier
- 9983985716902771
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