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Published on: March 6, 2018
PTEN knockout prostate cancer as a model for experimental immunotherapy
Kazunori Haga1, Atsushi Tomioka, Chun-Peng Liao
1Department of Medicine, University of California-Los Angeles, California, USA.
Purpose:
Testing immunotherapeutic strategies for prostate cancer has been impeded by the lack of relevant tumor models in immunocompetent animals. This opportunity is now provided by the recent development of prostate specific PTEN knockout mice, which show spontaneous development of true adenocarcinoma arising from prostate epithelium and more faithfully recapitulate the human disease than any previous model. We investigated the feasibility of using tumor cells derived from this model to test tumor vaccination and adoptive immunotherapeutic strategies for prostate cancer.
Materials And Methods:
PTEN-CaP8 adenocarcinoma cells derived from the biallelic PTEN knockout prostate cancer model were used to vaccinate nontumor bearing litter mates. Tumor specific effector cells were generated from splenocytes of vaccinated mice by mixed lymphocyte-tumor reactions, and antiproliferative effects and cytokine generation were examined in vitro. The effect of vaccination or adoptive immunotherapy on luciferase marked PTEN-CaP8 subcutaneous tumors was monitored by tumor volumetric measurements and noninvasive bioluminescence imaging.
Results:
Vaccination of litter mate mice with irradiated PTEN-CaP8 cells showed a significant prophylactic effect against the subsequent tumor challenge. Effector cells harvested from vaccinated litter mates showed significant interferon-gamma secretion upon co-incubation with PTEN-CaP8 target cells and they were capable of efficient target cell growth inhibition in vitro. Intratumor adoptive transfer of effector cells resulted in significant growth inhibition of preestablished prostate tumors in vivo.
Conclusions:
The PTEN knockout model serves as a highly useful model in which to investigate tumor cell vaccination and adoptive immunotherapeutic strategies in the context of true adenocarcinoma of the prostate. This model should accelerate efforts to develop effective immunotherapies for human prostate cancer.
Insights
A new PTEN knockout mouse model allows for testing prostate cancer immunotherapies. Vaccination and adoptive immunotherapy showed significant anti-tumor effects in this relevant model.
Area of Science:
- * Oncology
- * Immunology
- * Animal Models
Background:
- * Prostate cancer immunotherapy development is limited by suitable immunocompetent animal models.
- * PTEN knockout mice spontaneously develop prostate adenocarcinoma, closely mimicking human disease.
- * This model offers a novel platform for preclinical immunotherapy testing.
Purpose of the Study:
- * To evaluate the feasibility of using PTEN-CaP8 cells for prostate cancer vaccination.
- * To assess the efficacy of adoptive immunotherapy using effector cells from vaccinated mice.
- * To investigate tumor growth inhibition through vaccination and adoptive immunotherapy in vivo.
Main Methods:
- * PTEN-CaP8 adenocarcinoma cells from PTEN knockout mice were used for vaccination.
- * Effector cells were generated via mixed lymphocyte-tumor reactions and analyzed in vitro.
- * Tumor growth was monitored using bioluminescence imaging and volumetric measurements.
Main Results:
- * Vaccination demonstrated significant prophylactic effects against tumor challenge.
- * Effector cells secreted interferon-gamma and inhibited tumor cell growth in vitro.
- * Adoptive transfer of effector cells significantly inhibited established prostate tumors in vivo.
Conclusions:
- * The PTEN knockout model is highly effective for studying prostate cancer adenocarcinoma.
- * This model is crucial for advancing the development of effective immunotherapies for prostate cancer.
- * The findings support the acceleration of clinical translation for prostate cancer immunotherapies.
