DNA vaccines to target the cancer testis antigen PASD1 in human multiple myeloma

Area of Science:

• Immunology
• Oncology
• Vaccinology

Background:

• PASD1 is a cancer testis antigen found in multiple myeloma (MM) and persists after therapy.
• This persistence suggests targeting PASD1 with vaccines could be effective in treating minimal residual disease (MRD).

Purpose of the Study:

• To evaluate the efficacy of DNA fusion gene vaccines encoding PASD1 epitopes in a mouse model of MM.
• To assess the ability of these vaccines to induce anti-tumor immunity and cytotoxic T-lymphocyte (CTL) responses.

Main Methods:

• Development of DNA vaccines coupling tetanus toxin fragment C (DOM) with PASD1 sequences, including specific epitopes (p.DOM-PASD1(1), p.DOM-PASD1(2)) and full-length PASD1 (p.DOM-PASD1FL).
• Testing vaccine efficacy in Human Leukocyte Antigen (HLA)-A2 (HHD) transgenic mice using a human MM cell line.
• Assessing T-cell responses, CTL induction, and tumor cell lysis via in vitro and in vivo experiments.

Main Results:

• The p.DOM-PASD1(1) vaccine demonstrated superior T-cell induction and ability to lyse target cells compared to p.DOM-PASD1(2).
• Electroporation boosting significantly enhanced the response to p.DOM-PASD1(1).
• The full-length p.DOM-PASD1FL vaccine induced immunodominant PASD1(1) responses and mediated killing of native MM cells, indicating efficient antigen processing and presentation.

Conclusions:

• PASD1-derived epitopes are effectively processed and presented by human MM cells.
• PASD1-encoding DNA vaccines, particularly those targeting the PASD1(1) epitope, are a viable therapeutic strategy for MM, especially in the context of MRD.
• These findings support the clinical application of PASD1-based DNA vaccine therapy for multiple myeloma.