Abstract
BackgroundTesticular 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.MethodsTo 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.ResultsWe 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.ConclusionsConsidering 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.
Highlights
Testicular cancer is the most common male neoplasm occurring in men between the ages of 20 and 34
We found that vaccination with the p215-234 immunodominant peptide of mouse inhibin-α (Inα 215-234) provides significant inhibition of autochthonous testicular stromal cell (TSC) tumor growth occurring spontaneously in SJL.anti-Müllerian hormone (AMH)-SV40 proto-oncogene encoding the large transforming antigen (SV40Tag) transgenic mice
Generation of recombinant mouse inhibin-α Total RNA was purified from testes of 8 week old BALB/c male mice using the RNeasy Mini Kit (Qiagen, Valencia, CA), and the RNA was stabilized in RNAlater (Qiagen). cDNA was generated with random hexamers using the SuperScript III First-Strand Synthesis SuperMix (ThermoFisher Scientific, Waltham, MA)
Summary
Testicular cancer is the most common male neoplasm occurring in men between the ages of 20 and 34. 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. The vast majority of testicular cancers are germ cell tumors that have a 5-year overall survival rate exceeding 95% when treated early with surgery, chemotherapy, and/or radiation therapy [1, 2]. Several studies indicate that inhibin-α is a Aguilar et al Journal for ImmunoTherapy of Cancer (2017) 5:37 useful marker for human TSC tumors with intense immunohistochemical staining of inhibin-α occurring typically in >90% of Leydig and Sertoli cell tumors but in only about 10% of testicular germ cell tumors [5, 8, 9]. Inhibin-α stands out prominently as a potentially useful vaccine target for providing immunotherapy against TSC tumors
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
