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Therapeutic vaccination against a murine lymphoma by intratumoral injection of a cationic anticancer peptide

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Abstract

Cationic antimicrobial peptides (CAPs) exhibit promising anticancer activities. In the present study, we have examined the in vivo antitumoral effects of a 9-mer peptide, LTX-302, which is derived from the CAP bovine lactoferricin (LfcinB). A20 B cell lymphomas of BALB/c origin were established by subcutaneous inoculation in syngeneic mice. Intratumoral LTX-302 injection resulted in tumor necrosis and infiltration of inflammatory cells followed by complete regression of the tumors in the majority of the animals. This effect was T cell dependent, since the intervention was inefficient in nude mice. Successfully treated mice were protected against rechallenge with A20 cells, but not against Meth A sarcoma cells. Tumor resistance could be adoptively transferred with spleen cells from LTX-302-treated mice. Resistance was abrogated by depletion of T lymphocytes, or either the CD4+ or CD8+ T cell subsets. Taken together, these data suggest that LTX-302 treatment induced long-term, specific cellular immunity against the A20 lymphoma and that both CD4+ and CD8+ T cells were required. Thus, intratumoral administration of lytic peptide might, in addition to providing local tumor control, confer a novel strategy for therapeutic vaccination against cancer.

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Acknowledgments

This work was funded by a grant from the Norwegian Research Council and Lytix Biopharma. We thank Ragnhild Osnes for her technical assistance at the Animal Department. The staff at the Department of Electron Microscopy is acknowledged for their assistance. Kristel Berg and Inger Lindin at the Tunor Biology Research Group are acknowledged for their technical assistance during this work.

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Authors and Affiliations

  1. Tumor Biology Research Group, IMB, University of Tromsø, Tromsø, Norway

    Gerd Berge, Liv Tone Eliassen, Ketil Andre Camilio & Øystein Rekdal

  2. Lytix Biopharma, Tromsø Science Park, PO. Box 6447, 9294, Tromsø, Norway

    Liv Tone Eliassen, Ketil Andre Camilio & Øystein Rekdal

  3. Department of Cardiothoracic and Vascular Surgery, University Hospital North Norway, Tromsø, Norway

    Kristian Bartnes

  4. Division of Immunology, IMB, University of Tromsø, Tromsø, Norway

    Gerd Berge & Baldur Sveinbjørnsson

  5. Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden

    Baldur Sveinbjørnsson

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  1. Gerd Berge
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  2. Liv Tone Eliassen
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  3. Ketil Andre Camilio
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  5. Baldur Sveinbjørnsson
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  6. Øystein Rekdal
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Correspondence to Øystein Rekdal.

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Berge, G., Eliassen, L.T., Camilio, K.A. et al. Therapeutic vaccination against a murine lymphoma by intratumoral injection of a cationic anticancer peptide. Cancer Immunol Immunother 59, 1285–1294 (2010). https://doi.org/10.1007/s00262-010-0857-6

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  • DOI: https://doi.org/10.1007/s00262-010-0857-6

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