Generation of effective cancer vaccines genetically engineered to secrete cytokines using adenovirus-enhanced transferrinfection (AVET)

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

doi:10.1016/s0378-1119(96)00537-9

Cited by 14 publications

(8 citation statements)

References 5 publications

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“…In addition to unmodified pLys200 and fpLys200, unmodified pLys16, pLys450, and a different polycation, polyarginine pArg720, were tested. As a positive control, a cellular vaccine secreting GM-CSF was applied (32). Again, control groups receiving the peptide mix in IFA or without any adjuvant were also included.…”

Section: Resultsmentioning

confidence: 99%

“…Evidence from both bone marrow transplantation experiments (41) and histological investigations (32,42,43) in the murine system suggests the following working hypothesis for the events leading to the generation of cellular antitumor immunity. In the case of cellular cytokine-secreting irradiated vaccines, macrophage-like cells invade the vaccine deposit of irradiated cells and phagocytose the tumor cells within a relatively short period of days.…”

Section: Discussionmentioning

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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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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“…Schmidt et al [11], for example, tested a tumor vaccine whose cells expressed GM-CSF. This vaccine induced an antitumor immunity in 80% of the innoculated animals.…”

Section: Discussionmentioning

confidence: 99%

Relationships of Cytokine (Gm-Csf) Serum Concentration to Blood Cell Count and the Inflammatory Parameters in Children With Malignant Diseases

Müller

Mukodzi

Reddemann

1999

Pediatric Hematology and Oncology

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This study examined both the endogenous and exogenous (therapy-related) pharmacokinetics of the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) in neutropenic children with solid and systemic malignancies. The daily endogenous GM-CSF serum concentration before application was 29 pg/mL. During the 10 days of examination, the concentration rose to an average value of 1351 pg/mL 8 h after application. A significant stimulation of the neutrophils, monocytes, and eosinophils in peripheral blood was documented. No significant correlation between the GM-CSF concentration and peripheral blood cell counts could be documented. Paraclinically, there was no evidence for functional disturbance of either the liver or the kidneys, i.e., under the cytokine therapy. The therapy was well tolerated by all the children involved in the study.

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“…When administered intradermally with vaccine, GM-CSF elicits strong delayed-type hypersensitivity reactions to peptide antigens . A number of small, uncontrolled clinical vaccine trials that either used GM-CSF as an immune stimulant or engineered tumor cells to secrete GM-CSF showed encouraging preliminary results in the treatment of solid tumors, including melanoma, breast carcinoma, pancreatic cancer, renal cell carcinoma, non-small cell lung cancer (NSCLC), and prostate cancer (Schmidt et al 1997;Simons et al 1997;Hung et al 1998;Soiffer et al 1998;Disis et al 1999;Gaudernack and Gjertsen 1999;Leong et al 1999). Moreover, preclinical data suggested that optimal responses were achieved only with the use of GM-CSF.…”

Section: Granulocyte-macrophage Colony-stimulating Factor (Gm-csf)mentioning

confidence: 99%

Novel Technologies for Vaccine Development

Lukashevich¹,

Shirwan²

2014

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Generation of effective cancer vaccines genetically engineered to secrete cytokines using adenovirus-enhanced transferrinfection (AVET)

Cited by 14 publications

References 5 publications

Cell-free tumor antigen peptide-based cancer vaccines

Cell-free tumor antigen peptide-based cancer vaccines

Relationships of Cytokine (Gm-Csf) Serum Concentration to Blood Cell Count and the Inflammatory Parameters in Children With Malignant Diseases

Novel Technologies for Vaccine Development

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