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Published on: March 13, 2013
Using virally expressed melanoma cDNA libraries to identify tumor-associated antigens that cure melanoma
Jose Pulido1, Timothy Kottke, Jill Thompson
1Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA.
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.
Insights
Researchers used a vesicular stomatitis virus (VSV)-cDNA library to identify melanoma tumor rejection antigens. A combination of three identified antigens effectively eradicated established tumors in mice, demonstrating a novel approach to cancer immunotherapy.
Area of Science:
- Immunology
- Oncology
- Virology
Background:
- Melanoma tumor eradication can be achieved through immunotherapy.
- Identifying effective tumor rejection antigens is crucial for developing new cancer treatments.
Purpose of the Study:
- To identify tumor rejection antigens capable of inducing a tumor-specific CD4(+) interleukin-17 (IL-17) recall response.
- To evaluate the efficacy of a combination of identified antigens against established melanoma tumors in a mouse model.
Main Methods:
- A cDNA library derived from human melanoma cell lines was expressed using the vesicular stomatitis virus (VSV) vector.
- Mice with established melanoma tumors received multiple intravenous injections of the VSV-cDNA library.
- Tumor-specific IL-17 recall response was used to screen the library and identify effective VSV-cDNA virus clones.
Main Results:
- Intravenous injections of the VSV-cDNA library eradicated established melanoma tumors in mice.
- Tumor eradication correlated with a tumor-specific CD4(+) IL-17 recall response.
- Three specific VSV-cDNA virus clones, when used in combination, demonstrated efficacy comparable to the complete library in eradicating tumors.
Conclusions:
- VSV-expressed cDNA libraries are effective tools for identifying cooperating tumor rejection antigens.
- This approach can be applied to antigen discovery for various cancers and other immune-mediated diseases.
- The identified antigens hold potential for developing novel cancer immunotherapies.
