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Generation of Multivirus-specific T Cells to Prevent/treat Viral Infections after Allogeneic Hematopoietic Stem Cell Transplant
Published on: May 27, 2011
DNA immunotherapy targeting BARF1 induces potent anti-tumor responses against Epstein-Barr-virus-associated
Xizhou Zhu1, Alfredo Perales-Puchalt1, Krzysztof Wojtak1
1Vaccine and Immunotherapy Center, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Abstract:
Latent Epstein-Barr virus (EBV) infection is associated with several types of cancer. Several clinical studies have targeted EBV antigens as immune therapeutic targets with limited efficacy of EBV malignancies, suggesting that additional targets might be important. BamHI-A rightward frame 1 (BARF1) is an EBV antigen that is highly expressed in EBV+ nasopharyngeal carcinoma (NPC) and EBV-associated gastric carcinoma (EBVaGC). BARF1 antigen can transform human epithelial cells in vivo. BARF1-specific antibodies and cytotoxic T cells were detected in some EBV+ NPC patients. However, BARF1 has not been evaluated as an antigen in the context of therapeutic immunization. Its possible importance in this context is unclear. Here, we developed a synthetic-DNA-based expression cassette as immunotherapy targeting BARF1 (pBARF1). Immunization with pBARF1 induced potent antigen-specific humoral and T cell responses in vivo. Immunization with pBARF1 plasmid impacted tumor progression through the induction of CD8+ T cells in novel BARF1+ carcinoma models. Using an in vivo imaging system, we observed that pBARF1-immunized animals rapidly cleared cancer cells. We demonstrated that pBARF1 can induce antigen-specific immune responses that can impact cancer progression. Further study of this immune target is likely important as part of therapeutic approaches for EBV+ malignancies.
Insights
A novel DNA-based immunotherapy targeting the Epstein-Barr virus (EBV) antigen BARF1 (pBARF1) effectively generated immune responses and reduced tumor progression in preclinical models, suggesting BARF1 as a promising therapeutic target for EBV-associated cancers.
Area of Science:
- Immunology
- Oncology
- Virology
Background:
- Latent Epstein-Barr virus (EBV) infection is linked to various cancers.
- Current EBV-targeted immunotherapies show limited efficacy, indicating a need for new targets.
- The EBV antigen BARF1 is highly expressed in EBV-positive nasopharyngeal and gastric carcinomas and can transform cells.
Purpose of the Study:
- To evaluate BARF1 as a potential antigen for therapeutic immunization against EBV-associated malignancies.
- To develop and assess a synthetic DNA-based expression cassette targeting BARF1 (pBARF1) for immunotherapy.
Main Methods:
- Developed a synthetic DNA-based expression cassette (pBARF1) for immunotherapy.
- Administered pBARF1 immunization in preclinical models.
- Assessed antigen-specific humoral and T-cell responses (including CD8+ T cells).
- Utilized in vivo imaging to monitor tumor progression and cancer cell clearance.
Main Results:
- pBARF1 immunization induced robust antigen-specific humoral and T-cell immune responses in vivo.
- Immunization with pBARF1 impacted tumor progression by inducing CD8+ T cells in BARF1+ carcinoma models.
- pBARF1-treated animals showed rapid clearance of cancer cells, as observed via in vivo imaging.
Conclusions:
- pBARF1 can elicit antigen-specific immune responses capable of impacting cancer progression.
- BARF1 is a potential therapeutic target for EBV-associated malignancies.
- Further investigation of BARF1-based immunotherapy is warranted for EBV+ cancers.
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