Tumor eradication by immunotherapy with biodegradable PLGA microspheres : an alternative to incomplete Freund's adjuvant

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International Journal of Cancer. 2011, 129(2), pp. 407-416. ISSN 0020-7136. eISSN 1097-0215. Available under: doi: 10.1002/ijc.25914
Zusammenfassung

In experimental tumor immunotherapy, incomplete Freund's adjuvant (IFA) has been considered as the “gold standard” for T-cell vaccination in mice and humans in spite of its considerable adverse effects. Recently, we succeeded in eliciting strong CTL responses in mice after vaccination with biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microspheres (MS). In our study, we compared the immune response to IFA and PLGA-MS containing ovalbumin (OVA) and CpG-oligodeoxynucleotide (MS-OVA/CpG) or we used a mixture of MS-OVA/CpG and MS-polyI:C. A single vaccination with MS-OVA/CpG elicited long-lasting titers of IgG1 and IgG2a, but only low IgE titers, and also the T-cell response was biased toward Th1 differentiation. Antigen presentation to CD4+ and CD8+ cells and activation of a cytotoxic T-cell response in mice vaccinated with PLGA-MS and IFA lasted for over 3 weeks. Preconditioning of the injection site with TNF-α and heterologous prime-boost regimen further enhanced the cytotoxic response. PLGA-MS were as efficient or superior to IFA in eradication of preexisting tumors and suppression of lung metastases. Taken together, PLGA-MS are well-defined, biodegradable and clinically compatible antigen carrier systems that compare favorably with IFA in their efficacy of tumor immunotherapy in mouse models and hence deserve to be tested for their effectiveness against human malignant diseases.

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Fachgebiet (DDC)
570 Biowissenschaften, Biologie
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Microspheres, incomplete Freund's adjuvant, stimulation of T-cell proliferation, in vivo cytotoxicity, cancer
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ISO 690MÜLLER, Marc, Eva SCHLOSSER, Bruno GANDER, Marcus GRÖTTRUP, 2011. Tumor eradication by immunotherapy with biodegradable PLGA microspheres : an alternative to incomplete Freund's adjuvant. In: International Journal of Cancer. 2011, 129(2), pp. 407-416. ISSN 0020-7136. eISSN 1097-0215. Available under: doi: 10.1002/ijc.25914
BibTex
@article{Muller2011-07-15Tumor-16315,
  year={2011},
  doi={10.1002/ijc.25914},
  title={Tumor eradication by immunotherapy with biodegradable PLGA microspheres : an alternative to incomplete Freund's adjuvant},
  number={2},
  volume={129},
  issn={0020-7136},
  journal={International Journal of Cancer},
  pages={407--416},
  author={Müller, Marc and Schlosser, Eva and Gander, Bruno and Gröttrup, Marcus}
}
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