Using virally expressed melanoma cDNA libraries to identify tumor-associated antigens that cure melanoma

Jose Pulido; Timothy Kottke; Jill Thompson; Feorillo Galivo; Phonphimon Wongthida; Rosa Maria Diaz; Diana Rommelfanger; Elizabeth Ilett; Larry Pease; Hardev Pandha; Kevin Harrington; Peter Selby; Alan Melcher; Richard Vile

doi:10.1038/nbt.2157

Using virally expressed melanoma cDNA libraries to identify tumor-associated antigens that cure melanoma

Jose Pulido, Timothy Kottke, Jill Thompson, Feorillo Galivo, Phonphimon Wongthida, Rosa Maria Diaz, Diana Rommelfanger, Elizabeth Ilett, Larry Pease, Hardev Pandha, Kevin Harrington, Peter Selby, Alan Melcher, Richard Vile

Research output: Contribution to journal › Article › peer-review

75 Scopus citations

Abstract

Multiple intravenous injections of a cDNA library, derived from human melanoma cell lines and expressed using the highly immunogenic vector vesicular stomatitis virus (VSV), cured mice with established melanoma tumors. Successful tumor eradication was associated with the ability of mouse lymphoid cells to mount a tumor-specific CD4 ⁺ interleukin (IL)-17 recall response in vitro. We used this characteristic IL-17 response to screen the VSV-cDNA library and identified three different VSV-cDNA virus clones that, when used in combination but not alone, achieved the same efficacy against tumors as the complete parental virus library. VSV-expressed cDNA libraries can therefore be used to identify tumor rejection antigens that can cooperate to induce anti-tumor responses. This technology should be applicable to antigen discovery for other cancers, as well as for other diseases in which immune reactivity against more than one target antigen contributes to disease pathology.

Original language	English (US)
Pages (from-to)	337-343
Number of pages	7
Journal	Nature biotechnology
Volume	30
Issue number	4
DOIs	https://doi.org/10.1038/nbt.2157
State	Published - Apr 2012

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

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10.1038/nbt.2157

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title = "Using virally expressed melanoma cDNA libraries to identify tumor-associated antigens that cure melanoma",

abstract = "Multiple intravenous injections of a cDNA library, derived from human melanoma cell lines and expressed using the highly immunogenic vector vesicular stomatitis virus (VSV), cured mice with established melanoma tumors. Successful tumor eradication was associated with the ability of mouse lymphoid cells to mount a tumor-specific CD4 + interleukin (IL)-17 recall response in vitro. We used this characteristic IL-17 response to screen the VSV-cDNA library and identified three different VSV-cDNA virus clones that, when used in combination but not alone, achieved the same efficacy against tumors as the complete parental virus library. VSV-expressed cDNA libraries can therefore be used to identify tumor rejection antigens that can cooperate to induce anti-tumor responses. This technology should be applicable to antigen discovery for other cancers, as well as for other diseases in which immune reactivity against more than one target antigen contributes to disease pathology.",

author = "Jose Pulido and Timothy Kottke and Jill Thompson and Feorillo Galivo and Phonphimon Wongthida and Diaz, {Rosa Maria} and Diana Rommelfanger and Elizabeth Ilett and Larry Pease and Hardev Pandha and Kevin Harrington and Peter Selby and Alan Melcher and Richard Vile",

note = "Funding Information: We thank T. Higgins for expert secretarial assistance. This work was supported by the Richard M. Schulze Family Foundation, the Mayo Foundation, Cancer Research UK, the US National Institutes of Health grants R01 CA107082, R01CA130878 and R01 CA132734, and a grant from Terry and Judith Paul. MyD88 KO mice (MyD88−/−) were a kind gift from L. Pease, Mayo Clinic.",

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doi = "10.1038/nbt.2157",

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AU - Kottke, Timothy

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AU - Diaz, Rosa Maria

AU - Rommelfanger, Diana

AU - Ilett, Elizabeth

AU - Pease, Larry

AU - Pandha, Hardev

AU - Harrington, Kevin

AU - Selby, Peter

AU - Melcher, Alan

AU - Vile, Richard

N1 - Funding Information: We thank T. Higgins for expert secretarial assistance. This work was supported by the Richard M. Schulze Family Foundation, the Mayo Foundation, Cancer Research UK, the US National Institutes of Health grants R01 CA107082, R01CA130878 and R01 CA132734, and a grant from Terry and Judith Paul. MyD88 KO mice (MyD88−/−) were a kind gift from L. Pease, Mayo Clinic.

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N2 - Multiple intravenous injections of a cDNA library, derived from human melanoma cell lines and expressed using the highly immunogenic vector vesicular stomatitis virus (VSV), cured mice with established melanoma tumors. Successful tumor eradication was associated with the ability of mouse lymphoid cells to mount a tumor-specific CD4 + interleukin (IL)-17 recall response in vitro. We used this characteristic IL-17 response to screen the VSV-cDNA library and identified three different VSV-cDNA virus clones that, when used in combination but not alone, achieved the same efficacy against tumors as the complete parental virus library. VSV-expressed cDNA libraries can therefore be used to identify tumor rejection antigens that can cooperate to induce anti-tumor responses. This technology should be applicable to antigen discovery for other cancers, as well as for other diseases in which immune reactivity against more than one target antigen contributes to disease pathology.

AB - Multiple intravenous injections of a cDNA library, derived from human melanoma cell lines and expressed using the highly immunogenic vector vesicular stomatitis virus (VSV), cured mice with established melanoma tumors. Successful tumor eradication was associated with the ability of mouse lymphoid cells to mount a tumor-specific CD4 + interleukin (IL)-17 recall response in vitro. We used this characteristic IL-17 response to screen the VSV-cDNA library and identified three different VSV-cDNA virus clones that, when used in combination but not alone, achieved the same efficacy against tumors as the complete parental virus library. VSV-expressed cDNA libraries can therefore be used to identify tumor rejection antigens that can cooperate to induce anti-tumor responses. This technology should be applicable to antigen discovery for other cancers, as well as for other diseases in which immune reactivity against more than one target antigen contributes to disease pathology.

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Using virally expressed melanoma cDNA libraries to identify tumor-associated antigens that cure melanoma

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