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Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice
Published on: June 12, 2021
Control of mesothelin-expressing ovarian cancer using adoptive transfer of mesothelin peptide-specific CD8+ T cells
1Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA. chung2@jhmi.edu
Abstract:
Cancer immunotherapy targeting mesothelin represents a potentially plausible approach for the control of ovarian cancer as most ovarian cancers express high levels of mesothelin. In the current study, we created a mesothelin-positive luciferase-expressing ovarian cancer model, MOSEC/luc. This luciferase-expressing tumor model allowed us to quantitate tumor distribution and tumor load in tumor-challenged mice using a non-invasive bioluminescence imaging system. In addition, we identified an H-2D(b)-restricted mesothelin peptide-specific cytotoxic T-lymphocyte (CTL) epitope (amino acid (aa) 406-414) that was endogenously processed and presented by MOSEC/luc tumor cells. We showed that adoptive transfer of mesothelin peptide (aa406-414)-specific CD8(+) T cells led to the control of MOSEC/luc tumor cells. The MOSEC/luc tumor model and the newly identified H-2D(b)-restricted murine mesothelin-specific CTL epitope (aa406-414) will be very useful for the development of immunotherapy for ovarian cancer as well as for the development of quantitative CD8(+) T cell-mediated immunological assays.
Insights
Researchers developed a new ovarian cancer model to test immunotherapy. They identified a specific mesothelin peptide that, when targeted by CD8(+) T cells, effectively controlled tumor growth in mice.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Ovarian cancer often overexpresses mesothelin, a potential target for immunotherapy.
- Developing effective immunotherapies requires precise models to study tumor behavior and immune response.
Purpose of the Study:
- To create a novel, quantifiable ovarian cancer model for immunotherapy research.
- To identify a specific mesothelin peptide epitope for T cell-mediated immune responses.
- To evaluate the therapeutic potential of targeting this mesothelin epitope in ovarian cancer.
Main Methods:
- Generation of a mesothelin-positive, luciferase-expressing ovarian cancer cell line (MOSEC/luc).
- Utilized non-invasive bioluminescence imaging to monitor tumor progression in vivo.
- Identified an H-2D(b)-restricted mesothelin peptide epitope (aa 406-414).
- Performed adoptive transfer of mesothelin peptide-specific CD8(+) T cells in tumor-bearing mice.
Main Results:
- The MOSEC/luc model enabled accurate quantification of tumor load and distribution.
- An endogenous, H-2D(b)-restricted mesothelin peptide epitope (aa 406-414) was identified.
- Adoptive transfer of specific CD8(+) T cells resulted in significant control of MOSEC/luc tumors.
- Demonstrated the feasibility of targeting this epitope for ovarian cancer immunotherapy.
Conclusions:
- The MOSEC/luc model is a valuable tool for preclinical immunotherapy studies in ovarian cancer.
- The identified mesothelin epitope and associated T cell response provide a basis for developing targeted immunotherapies.
- This research supports the advancement of CD8(+) T cell-mediated immunological assays for ovarian cancer treatment strategies.
