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Vaccines targeting the cancer-testis antigen SSX-2 elicit HLA-A2 epitope-specific cytolytic T cells

Heath A Smith1, Douglas G McNeel

  • 1Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.

Journal of Immunotherapy (Hagerstown, Md. : 1997)
|September 10, 2011
PubMed

Insights

A DNA vaccine targeting the SSX-2 antigen identified an immunodominant epitope (p103-111) that elicits cancer-killing T cells. These SSX-2 specific T cells were found in prostate cancer patients, suggesting potential for immunotherapy.

Area of Science:

  • Immunology
  • Oncology
  • Vaccine Development

Background:

  • The cancer-testis antigen synovial sarcoma X breakpoint-2 (SSX-2) is expressed in germline cells and frequently in cancers, making it a potential target for cancer immunotherapy.
  • Human leukocyte antigen (HLA)-A2 is a common allele, and identifying HLA-A2-restricted SSX-2 epitopes is crucial for developing effective vaccines for HLA-A2+ patients.

Purpose of the Study:

  • To evaluate a genetic vaccine encoding SSX-2 for its ability to elicit SSX-2-specific cytotoxic T lymphocytes (CTLs).
  • To prioritize HLA-A2-specific epitopes of SSX-2 and assess their potential to induce CTLs capable of lysing prostate cancer cells.

Main Methods:

  • Identification of HLA-A2-restricted SSX-2 epitopes based on in vitro binding affinity and immunogenicity in HLA-A2 transgenic mice.
  • Vaccination of transgenic mice with a DNA plasmid encoding SSX-2 to assess immune responses.
  • Assessment of CTL-mediated lysis of prostate cancer cells and detection of SSX-2 epitope-specific CTLs in patient peripheral blood.

Main Results:

  • Two SSX-2 peptides, p41-49 and p103-111, showed high HLA-A2 binding affinity and in vivo immunogenicity.
  • Peptide p103-111 was found to be immunodominant, eliciting robust peptide-specific immune responses after DNA vaccination.
  • p103-111-specific CTLs effectively lysed an HLA-A2+ prostate cancer cell line, and these epitope-specific CTLs were detectable in HLA-A2+ prostate cancer patients.

Conclusions:

  • SSX-2 peptide p103-111 is an immunodominant, HLA-A2-restricted epitope with potential for prostate cancer immunotherapy.
  • The presence of SSX-2 epitope-specific CD8 T cells in prostate cancer patients suggests that immune tolerance to SSX-2 can be overcome.
  • These findings support SSX-2 as a relevant target antigen for developing prostate cancer vaccine strategies.

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