Coencapsulation of tumor lysate and CpG-ODN in PLGA-microspheres enables successful immunotherapy of prostate carcinoma in TRAMP mice

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2012
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Journal of Controlled Release. 2012, 162(1), pp. 159-166. ISSN 0168-3659. eISSN 1873-4995. Available under: doi: 10.1016/j.jconrel.2012.06.015
Zusammenfassung

Biodegradable poly(lactide-co-glycolide) (PLGA) microspheres (MS) deliver antigens and toll like receptor (TLR) ligands to antigen presenting cells (APC) in vitro and in vivo. PLGA-MS-microencapsulated model antigens are efficiently presented on MHC class I and II molecules of dendritic cells and stimulate strong cytotoxic and T helper cell responses enabling the eradication of pre-existing model tumors. The application of tumor lysates as a source of antigen for immunotherapy has so far not been very successful also due to a lack of suitable delivery systems. In this study we used PLGA-MS with co-encapsulated tumor lysates and CpG oligodeoxynucleotides (CpG-ODN) as well as microencapsulated polyI:C in order to elicit anti-tumor responses. Immunization of mice with such mixtures of MS yielded substantial cytotoxic T cell (CTL) responses and interfered with tumor growth in TRAMP mice, a pre-clinical transgenic mouse model of prostate carcinoma, which has previously resisted dendritic cell‐based therapy. As an important step towards clinical application of PLGA-MS, we could show that γ-irradiation of PLGA-MS sterilized the MS, without reducing their efficacy in eliciting CTL and anti-tumor responses in subcutaneous tumor grafts. Since PLGA is approved for clinical application, sterilized PLGA-MS containing tumor ysates and TLR ligands hold promise as anti-tumor vaccines against prostate carcinoma in humans.

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Fachgebiet (DDC)
570 Biowissenschaften, Biologie
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Prostate cancer, TRAMP, PLGA microspheres, Tumor lysate
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ISO 690MÜLLER, Marc, Wilfried REICHARDT, Julia KÖRNER, Marcus GRÖTTRUP, 2012. Coencapsulation of tumor lysate and CpG-ODN in PLGA-microspheres enables successful immunotherapy of prostate carcinoma in TRAMP mice. In: Journal of Controlled Release. 2012, 162(1), pp. 159-166. ISSN 0168-3659. eISSN 1873-4995. Available under: doi: 10.1016/j.jconrel.2012.06.015
BibTex
@article{Muller2012-08-20Coenc-22000,
  year={2012},
  doi={10.1016/j.jconrel.2012.06.015},
  title={Coencapsulation of tumor lysate and CpG-ODN in PLGA-microspheres enables successful immunotherapy of prostate carcinoma in TRAMP mice},
  number={1},
  volume={162},
  issn={0168-3659},
  journal={Journal of Controlled Release},
  pages={159--166},
  author={Müller, Marc and Reichardt, Wilfried and Körner, Julia and Gröttrup, Marcus}
}
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