Vaccination with inhibin-α provides effective immunotherapy against testicular stromal cell tumors
Robert Aguilar1,2,3, Justin M Johnson1,2, Patrick Barrett1
1Department of Immunology, NB30, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195 USA.
Background:
Testicular cancer is the most common male neoplasm occurring in men between the ages of 20 and 34. Although germ-line testicular tumors respond favorably to current standard of care, testicular stromal cell (TSC) tumors derived from Sertoli cells or Leydig cells often fail to respond to chemotherapy or radiation therapy and have a 5-year overall survival significantly lower than the more common and more treatable germ line testicular tumors.
Methods:
To improve outcomes for TSC cancer, we have developed a therapeutic vaccine targeting inhibin-α, a protein produced by normal Sertoli and Leydig cells of the testes and expressed in the majority of TSC tumors.
Results:
We found that vaccination against recombinant mouse inhibin-α provides protection and therapy against transplantable I-10 mouse TSC tumors in male BALB/c mice. Similarly, we found that vaccination with the immunodominant p215-234 peptide of inhibin-α (Inα 215-234) inhibits the growth of autochthonous TSC tumors occurring in male SJL.AMH-SV40Tag transgenic mice. The tumor immunity and enhanced overall survival induced by inhibin-α vaccination may be passively transferred into naive male BALB/c recipients with either CD4+ T cells, B220+ B cells, or sera from inhibin-α primed mice.
Conclusions:
Considering the lack of any alternative effective treatment for chemo- and radiation-resistant TSC tumors, our results provide for the first time a rational basis for immune-mediated control of these aggressive and lethal variants of testicular cancer.
Insights
This study developed a novel therapeutic vaccine targeting inhibin-α for testicular stromal cell (TSC) tumors. This inhibin-α vaccine shows promise in controlling aggressive, treatment-resistant testicular cancers.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Testicular cancer is the most common male neoplasm in young men (20-34 years).
- Germ-line testicular tumors respond well to standard care.
- Testicular stromal cell (TSC) tumors are resistant to chemotherapy and radiation, with lower survival rates.
Purpose of the Study:
- To develop an improved therapeutic strategy for testicular stromal cell (TSC) tumors.
- To target inhibin-α, a protein expressed in most TSC tumors.
Main Methods:
- Developed a therapeutic vaccine targeting inhibin-α.
- Tested vaccine efficacy in mouse models of TSC tumors (transplantable and autochthonous).
- Investigated passive transfer of tumor immunity via T cells, B cells, or sera.
Main Results:
- Vaccination against recombinant mouse inhibin-α protected against and treated transplantable TSC tumors.
- Vaccination with the inhibin-α peptide (Inα 215-234) inhibited autochthonous TSC tumor growth.
- Tumor immunity and survival benefits were transferable via immune cells or sera.
Conclusions:
- Provides the first rational basis for immune-mediated control of aggressive TSC tumors.
- Highlights inhibin-α vaccination as a potential therapeutic approach for chemo- and radiation-resistant testicular cancers.
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