School of Medicine and Health Sciences Poster Presentations
Development and Optimization of a Recombinant Attenuated Salmonella Cancer Vaccine
Poster Number
21
Document Type
Poster
Publication Date
3-2016
Abstract
Background:
Treatment options for high risk neuroblastoma are desperately needed since surgical options for neuroblastoma are often limited, and chemotherapy has dose-limiting side effects. Immunotherapy in the form of vaccines are attractive alternatives as they will be more precise than current therapies and can potentially confer lifelong protection against relapse.
However, despite the promise of cancer vaccines, further improvements must be made. Circulating survivin-specific cytotoxic T lymphocytes (CTLs) are detectable at low levels in high-risk neuroblastoma patients at diagnosis and it is possible to expand surviving-specific CTLs ex vivo from healthy donors and cancer patients. These CTLs show in vitro cytotoxicity towards HLA matched survivin expressing tumors.
One promising FDA-approved vaccine strategy involves the use of attenuated Salmonella strains. Due to their adjuvant-like properties they can overcome the immuno-suppressive effects of the tumor microenvironment known to be a major cause of vaccine failure.
Objective:
Our goal is to utilize attenuated Salmonella vaccine strains as a method of achieving in vivo priming of APC and expansion of survivin specific CTLs as a vaccine for the treatment of high-risk neuroblastoma.
Methods:
An array of attenuated Salmonella strains expressing different phenotypes were manufactured and tailored to serve as vaccines to elicit survivin responses. A/J mice were immunized with RASVs, serum from treated animals were assayed for the presence of survivin antibodies and splenocytes were harvested to detect survivin-specific T cells.
Results and Future Plans:
Human and mouse survivin has been cloned and sequenced into 12 different candidate RASVs, and their expression verified. Animals injected with survivin protein were shown to express anti-survivin antibodies 28 days after treatment 100 fold higher than baseline levels. Current efforts are aimed at further screening of the RASVs. Candidate RASVs that produce significant cytokine and antibody responses will be tested in an immunocompetent mouse model of neuroblastoma using the cell line neuro-2a. Immune responses will be compared to mice given empty RASV and mice subcutaneously injected with a survivin protein/adjuvant emulsion.
Conclusion:
If this approach is successful it will produce candidate RASVs that may improve the survival rates of children with neuroblastoma.
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Open Access
1
Development and Optimization of a Recombinant Attenuated Salmonella Cancer Vaccine
Background:
Treatment options for high risk neuroblastoma are desperately needed since surgical options for neuroblastoma are often limited, and chemotherapy has dose-limiting side effects. Immunotherapy in the form of vaccines are attractive alternatives as they will be more precise than current therapies and can potentially confer lifelong protection against relapse.
However, despite the promise of cancer vaccines, further improvements must be made. Circulating survivin-specific cytotoxic T lymphocytes (CTLs) are detectable at low levels in high-risk neuroblastoma patients at diagnosis and it is possible to expand surviving-specific CTLs ex vivo from healthy donors and cancer patients. These CTLs show in vitro cytotoxicity towards HLA matched survivin expressing tumors.
One promising FDA-approved vaccine strategy involves the use of attenuated Salmonella strains. Due to their adjuvant-like properties they can overcome the immuno-suppressive effects of the tumor microenvironment known to be a major cause of vaccine failure.
Objective:
Our goal is to utilize attenuated Salmonella vaccine strains as a method of achieving in vivo priming of APC and expansion of survivin specific CTLs as a vaccine for the treatment of high-risk neuroblastoma.
Methods:
An array of attenuated Salmonella strains expressing different phenotypes were manufactured and tailored to serve as vaccines to elicit survivin responses. A/J mice were immunized with RASVs, serum from treated animals were assayed for the presence of survivin antibodies and splenocytes were harvested to detect survivin-specific T cells.
Results and Future Plans:
Human and mouse survivin has been cloned and sequenced into 12 different candidate RASVs, and their expression verified. Animals injected with survivin protein were shown to express anti-survivin antibodies 28 days after treatment 100 fold higher than baseline levels. Current efforts are aimed at further screening of the RASVs. Candidate RASVs that produce significant cytokine and antibody responses will be tested in an immunocompetent mouse model of neuroblastoma using the cell line neuro-2a. Immune responses will be compared to mice given empty RASV and mice subcutaneously injected with a survivin protein/adjuvant emulsion.
Conclusion:
If this approach is successful it will produce candidate RASVs that may improve the survival rates of children with neuroblastoma.
Comments
Presented at: GW Research Days 2016