Videos of Sipuleucel-T Programmed T Cells Lysing Cells That Express Prostate Cancer Target Antigens
Adam S Kibel1,2, Brant A Inman3, Russell K Pachynski4
1Affiliations of authors: Dana-Farber Cancer Institute, Boston, MA, USA.
Abstract:
Sipuleucel-T, an autologous cellular immunotherapy, was approved to treat metastatic castration-resistant prostate cancer in 2010 in the United States. Treatment with sipuleucel-T primes the immune system to target prostate acid phosphatase, which is expressed by prostate cancer cells, potentially leading to lysis of cancer cells. Expanding on previously reported indirect evidence of cell killing with sipuleucel-T treatment, we sought to provide direct evidence of cell lysis through visualization. We used advanced video technology and available samples of peripheral blood mononuclear cells from subjects enrolled in the STAMP trial (NCT01487863). Isolated CD8+ T cells were used as effector cells and cocultured with autologous monocytes pulsed with control or target antigens. Differentially stained effector and target cells were then video recorded during coculture. Here, we present video recordings and analyses of T cells from sipuleucel-T-treated subjects showing-for the first time-direct lysis of cells that express prostate cancer target antigens, prostate acid phosphatase, or prostate-specific antigen.
Insights
Sipuleucel-T immunotherapy directly kills prostate cancer cells expressing target antigens. This study provides the first visual evidence of T-cell mediated cancer cell lysis in patients treated with this prostate cancer therapy.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Sipuleucel-T is an autologous cellular immunotherapy approved for metastatic castration-resistant prostate cancer.
- It primes the immune system to target prostate acid phosphatase (PAP) on cancer cells, suggesting potential cell killing.
- Previous evidence for cell lysis was indirect.
Purpose of the Study:
- To provide direct visual evidence of T-cell mediated cancer cell lysis induced by Sipuleucel-T treatment.
- To analyze T-cell activity using advanced video technology on patient samples.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) from subjects in the STAMP trial were utilized.
- CD8+ T cells were isolated as effector cells and co-cultured with autologous monocytes pulsed with control or target antigens.
- Differentially stained cells were video recorded during co-culture to observe interactions.
Main Results:
- Direct lysis of target cells expressing prostate cancer antigens (PAP or PSA) by T cells from Sipuleucel-T treated subjects was visualized.
- This study presents the first direct video evidence of Sipuleucel-T mediated cancer cell killing.
Conclusions:
- Sipuleucel-T treatment leads to direct cytotoxic activity of T cells against prostate cancer cells.
- Visual confirmation of cell lysis supports the mechanism of action for Sipuleucel-T in prostate cancer therapy.
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