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Neoantigen-based EpiGVAX vaccine initiates antitumor immunity in colorectal cancer

Victoria M Kim1,2,3, Xingyi Pan1,2, Kevin C Soares1,3

  • 1The Sidney Kimmel Comprehensive Cancer Center.

JCI Insight
|May 8, 2020
PubMed

Insights

This study shows that epigenetic therapy using 5-aza-2'-deoxycytidine (DAC) can upregulate cancer testis antigens (CTAs) in metastatic colorectal cancer. Combining DAC with an epigenetically modified cancer vaccine (EpiGVAX) improved survival and enhanced anti-tumor immune responses.

Area of Science:

  • Immunology
  • Oncology
  • Epigenetics

Background:

  • Metastatic colorectal cancer (CRC) exhibits poor immunogenicity, limiting the effectiveness of current cancer vaccines.
  • Previous strategies to enhance neoantigen expression for cancer vaccines have shown limited success.

Purpose of the Study:

  • To investigate the role of DNA methyltransferase inhibitor (DNMTi) 5-aza-2 -deoxycytidine (DAC) in inducing cancer testis antigen (CTA) expression in CRC.
  • To evaluate the antitumor efficacy of combining DAC with an epigenetically regulated cancer vaccine (EpiGVAX).

Main Methods:

  • Utilized a murine model of metastatic CRC.
  • Administered combination therapy with an irradiated whole-cell CRC vaccine (GVAX) and DAC.
  • Assessed CTA expression and antitumor efficacy, including survival outcomes and immune responses.

Main Results:

  • DAC significantly induced CTA expression in CRC, including the novel CTA Tra-P1A.
  • The combination of EpiGVAX with DAC demonstrated improved survival outcomes compared to GVAX alone.
  • Enhanced antigen-specific antitumor immune responses were observed, potentially due to improved CTA expression.

Conclusions:

  • Epigenetic therapy with DNMTi (DAC) can induce CTA expression and sensitize tumor cells for immunotherapy in metastatic CRC.
  • Combining EpiGVAX with DAC enhances antitumor efficacy by promoting antigen-specific T cell responses to epigenetically regulated proteins.
Keywords:
Cancer immunotherapyColorectal cancerOncologyTherapeutics

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