Cancer vaccines: the interleukin 2 dosage effect.

Schmidt, W.; Schweighoffer, Tamás; Herbst, E; Maass, G.; Berger, M; Schilcher, F.; Schaffner, G.; Birnstiel, Max L.

doi:10.1073/pnas.92.10.4711

Cited by 123 publications

(74 citation statements)

References 15 publications

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“…It has been combining AvTK/ganciclovir with AvIL2 on tumor rejection compared with AvTK/ganciclovir therapy. Howreported that IL-2 expressed from tumor cells as a cancer vaccine has a concentration optimum 26 above which ILever, other investigations demonstrated an improved treatment outcome for combined application of 2 has inhibitory effects on tumor rejection. In our experiments, in vitro IL-2 secretion was in this therapeutic AvTK/ganciclovir treatment and recombinant Avs expressing IL-2.…”

Section: Nations Of Avs and Re-challenged With M-msv Or K-balb Tumor mentioning

confidence: 99%

Characterization of the antitumor immune response generated by treatment of murine tumors with recombinant adenoviruses expressing HSVtk, IL-2, IL-6 or B7-1

1997

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In a cancer gene therapy model recombinant adenoviruses challenge with wild-type tumor but not from challenges with expressing the herpes simplex virus thymidine kinase an unrelated syngeneic tumor cell line. Since cytotoxic T (HSVtk) gene were injected into tumors in situ, either alone lymphocyte responses in this tumor model were weak, we or in combination with adenoviruses (Avs) engineered to analyzed cytokine secretion from spleen cells of treated express IL-2, IL-6 or the costimulatory molecule B7-1.animals. The best correlate of antitumor immunity in this HSVtk phosphorylates the prodrug ganciclovir, thus conmodel was enhanced secretion of GM-CSF, while verting it into an antimetabolite which kills not only HSVtk secretion of IL-2, IL-6 and IFN␥ was also frequently expressing cells, but also by the 'bystander effect', neighincreased but not as consistently. The enhanced IFN␥ boring untransduced tumor cells. The tumors regressed in secretion associated with unchanged IL-4 secretion sug-80% of mice upon AvTK/ganciclovir treatment; combigests that AvTK treatment results in a predominantly Th1-nations with AvIL-2, AvIL-6, or AvB7-1 did not improve mediated antitumor immune response. these results. Cured mice were protected from further

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Section: Nations Of Avs and Re-challenged With M-msv Or K-balb Tumor mentioning

confidence: 99%

Characterization of the antitumor immune response generated by treatment of murine tumors with recombinant adenoviruses expressing HSVtk, IL-2, IL-6 or B7-1

1997

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“…These results suggest a certain, yet to date unidentified, optimal mGM-CSF dose. In 1995, Schmidt et al 46 described a similar IL-2 dosage effect. The findings may have considerable consequences for clinical application of cytokine-transduced, autologous tumor cell vaccines but also for production of the vaccines.…”

Section: Discussionmentioning

confidence: 92%

Replication-defective recombinant Semliki Forest virus encoding GM-CSF as a vector system for rapid and facile generation of autologous human tumor cell vaccines

et al. 2001

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“…Two of eight animals were protected when the pLys240 was used, and four of eight animals were protected when pLys16 was used. These results show that a single peptide, when applied with pLys as adjuvant, can evoke efficient antitumor protection comparable to that of one of the most potent cytokine-secreting whole-cell vaccines that has become the gold standard for antitumor vaccination (19,24). The selection of the peptide motifs was based on requirements for H-2K d -restricted anchor amino residues as described (16,(33)(34)(35)(36).…”

Section: Resultsmentioning

confidence: 99%

“…Constitutively GM-CSF-secreting P815 cells were generated upon Transfectam-mediated cotransfection of 10 g of pWS-GM-CSF (ref. 19; linearized with EcoRI) and 2 g of pRSVneo (linearized with XmnI; ref. 20) according to the manufacturer's protocol (Promega).…”

mentioning

confidence: 99%

“…Cells were routinely tested for mycoplasma contamination by a PCR-based mycoplasma detection kit (Stratagene). Transiently cytokine-secreting cellular vaccines were generated by the adenovirus-enhanced transferrinfection (AVET) technology, using the murine interleukin 2 (IL-2) and granulocytemacrophage colony stimulating factor (GM-CSF) expression vectors and the AVET protocol as described (19). In the M-3 system, expression levels were adjusted to optimal values (IL-2, 1000-2000 units͞10 5 cells; GM-CSF, Ն10 ng͞10 5 cells).…”

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confidence: 99%

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Cell-free tumor antigen peptide-based cancer vaccines

Schmidt

Buschle

Zauner

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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The central role that tumor antigen-derived peptides play in induction of antitumor immunity makes them ideal candidates for peptide-based cancer vaccines. We have demonstrated that ''transloading'' is an efficient strategy for importing short peptide ligands into antigen-presenting cells in vitro. Postulating that the transloading procedure might effect peptide uptake by antigen-presenting cells in vivo as well, we tested this approach for the generation of peptidebased cancer vaccines. In the P815 mastocytoma system, we vaccinated mice by s.c. injection of a single, known natural peptide derived from JAK-1 kinase. Whereas vaccination with peptide alone or mixed with incomplete Freund's adjuvant was ineffective, application of the peptide in conjunction with the polycation poly-L-lysine protected a significant number of animals against tumor challenge. Dependent upon the type of poly-L-lysine applied, protection against tumor take was comparable to that achieved with irradiated whole-cell vaccines, genetically modified to secrete granulocyte-macrophage colony-stimulating factor. In the murine melanoma M-3, a combination of four putative tumor antigen-derived peptides was tested as a cancer vaccine. Administered in combination with polycations, these peptides evoked potent antitumor immunity that could not be obtained with the peptides alone or peptides emulsified in incomplete Freund's adjuvant. However, peptide-polycation vaccines applied to the M-3 model were not as efficient as cellular control vaccines, consisting of irradiated interleukin 2 or granulocyte-macrophage colonystimulating factor-secreting tumor cells.

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Cancer vaccines: the interleukin 2 dosage effect.

Cited by 123 publications

References 15 publications

Characterization of the antitumor immune response generated by treatment of murine tumors with recombinant adenoviruses expressing HSVtk, IL-2, IL-6 or B7-1

Characterization of the antitumor immune response generated by treatment of murine tumors with recombinant adenoviruses expressing HSVtk, IL-2, IL-6 or B7-1

Replication-defective recombinant Semliki Forest virus encoding GM-CSF as a vector system for rapid and facile generation of autologous human tumor cell vaccines

Cell-free tumor antigen peptide-based cancer vaccines

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