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Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
Published on: April 21, 2022
Control of human mesothelin-expressing tumors by DNA vaccines
1Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
Abstract:
Mesothelin has been implicated as a potential ideal target antigen for the development of antigen-specific cancer immunotherapy for the control of mesothelin-expressing cancers such as ovarian cancer, mesothelioma and pancreatic adenocarcinoma. In the current study, we utilized a DNA vaccine encoding human mesothelin (pcDNA3-Hmeso) to treat C57BL/6 mice challenged with luciferase-expressing, Hmeso-expressing ovarian cancer cell line, Defb29 Vegf-luc/Hmeso. The therapeutic effect of the tumor-challenged mice was followed by noninvasive bioluminescence imaging systems. The mechanism of the antitumor effect was characterized by depletion of subsets of lymphocytes as well as adopted transfer of serum from pcDNA3-Hmeso-vaccinated mice. We found that vaccination with pcDNA3-Hmeso DNA vaccine generates a significant antitumor effect and promotes survival in mice challenged with Defb29 Vegf-luc/Hmeso. Furthermore, we found CD4+ and CD8+ T-cell immune responses as well as the humoral immune responses are important for the observed antitumor effects in vaccinated mice. Our data indicated that vaccination with DNA vaccine targeting Hmeso could generate potent antitumor effects against mesothelin-expressing tumors through both T cell-mediated immunity as well as antibody-mediated immunity.
Insights
A DNA vaccine targeting mesothelin (Hmeso) effectively controlled ovarian cancer in mice. This immunotherapy approach stimulated both T-cell and antibody immune responses, improving survival against mesothelin-expressing tumors.
Area of Science:
- Immunology
- Oncology
- Vaccinology
Background:
- Mesothelin is a promising target antigen for cancer immunotherapy.
- Mesothelin-expressing cancers include ovarian cancer, mesothelioma, and pancreatic adenocarcinoma.
Purpose of the Study:
- To evaluate the therapeutic efficacy of a DNA vaccine encoding human mesothelin (pcDNA3-Hmeso) against ovarian cancer in a preclinical mouse model.
- To elucidate the immunological mechanisms underlying the antitumor effects induced by the DNA vaccine.
Main Methods:
- C57BL/6 mice were challenged with Hmeso-expressing ovarian cancer cells (Defb29 Vegf-luc/Hmeso).
- Mice were vaccinated with the pcDNA3-Hmeso DNA vaccine.
- Tumor growth was monitored using noninvasive bioluminescence imaging.
- Immune responses were analyzed through lymphocyte depletion and serum adoptive transfer studies.
Main Results:
- Vaccination with pcDNA3-Hmeso significantly inhibited tumor growth and improved survival in mice.
- The antitumor effect was associated with both CD4+ and CD8+ T-cell immune responses.
- Humoral immune responses (antibody-mediated immunity) also contributed to the therapeutic outcome.
Conclusions:
- The pcDNA3-Hmeso DNA vaccine demonstrates potent therapeutic potential against mesothelin-expressing tumors.
- Effective antitumor immunity relies on a combination of T-cell-mediated and antibody-mediated responses.
- This study supports the development of mesothelin-targeted DNA vaccines for cancer immunotherapy.
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