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Modified DCs and MSCs with HPV E7 antigen and small Hsps: Which one is the most potent strategy for eradication of
Azam Bolhassani1, Sepideh Shahbazi1, Elnaz Agi2
1Department of Hepatitis and AIDs, Pasteur Institute of Iran, Tehran, Iran.
Abstract:
Immunotherapy with DCs as antigen-presenting vehicles have already improved patients' outcome against a variety of tumors. Moreover, MSCs were recently used to develop anti-cancer therapeutic or anti-microbial prophylactic vaccines. The current study evaluated immune responses and anti-tumor effects generated by DCs and MSCs derived from mouse bone marrow which were modified with small heat shock proteins 27 and 20 (sHsp27 and sHsp20) and also E7 oncoprotein in tumor mouse model. Two vaccination strategies were utilized including homologous DC or MSC prime/ DC or MSC boost, and heterologous MSC or DC prime/ protein boost vaccinations. Our data revealed that DCs pulsed with E7+Hsp27 and/or E7+Hsp20 in homologous and heterologous prime/ boost vaccinations could stimulate high levels of IgG2a, IgG2b, IFN-γ and IL-10 directed toward Th1 responses. Moreover, these regimens induced an increased level of Granzyme B, and displayed complete protection more than 60 days after treatment. On the other hand, MSCs transfected with E7+Hsp27 DNA in homologous and heterologous prime/ boost vaccinations could significantly enhance the E7-specific T-cell responses and suppress tumor growth in mice. However, MSCs transfected with E7+Hsp20 DNA did not induce a complete protection against TC-1 tumor compared to DCs pulsed with E7+Hsp20 protein complexes. These results indicated that DC- and MSC-based vaccinations with specific modalities will be a useful approach for immunotherapy and protection against HPV-associated cancers.
Insights
Dendritic cells (DCs) and mesenchymal stem cells (MSCs) modified with small heat shock proteins (sHsps) and E7 oncoprotein show promise for cancer immunotherapy. These modified cells effectively stimulate immune responses and provide significant protection against tumors in mouse models.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Dendritic cells (DCs) and mesenchymal stem cells (MSCs) are explored for cancer immunotherapy.
- Small heat shock proteins (sHsps) and oncoproteins are investigated as vaccine components.
Purpose of the Study:
- To evaluate immune responses and anti-tumor effects of DCs and MSCs modified with sHsp27, sHsp20, and E7 oncoprotein.
- To compare homologous and heterologous prime/boost vaccination strategies.
Main Methods:
- DCs and MSCs were derived from mouse bone marrow.
- Cells were modified with sHsp27, sHsp20, and E7 oncoprotein.
- Homologous and heterologous prime/boost vaccination strategies were employed in a tumor mouse model.
Main Results:
- DCs pulsed with E7+Hsp27/Hsp20 induced Th1 responses (IgG2a, IgG2b, IFN-γ, IL-10) and complete tumor protection.
- MSCs transfected with E7+Hsp27 enhanced E7-specific T-cell responses and suppressed tumor growth.
- MSCs transfected with E7+Hsp20 did not achieve complete protection.
Conclusions:
- DC- and MSC-based vaccinations with specific modalities are effective for immunotherapy against HPV-associated cancers.
- The choice of cell type and modification strategy impacts therapeutic efficacy.
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