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Photodynamic therapy-generated cancer vaccine elicits acute phase and hormonal response in treated mice
Mladen Korbelik1, Soroush Merchant
1British Columbia Cancer Agency, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada. mkorbelik@bccrc.ca
Abstract:
Photodynamic therapy (PDT)-generated cancer vaccines have shown promising results in preclinical studies and are being introduced in the clinics. Using an SCCVII mouse squamous cell carcinoma-based whole-cell autologous PDT vaccine model developed in our previous work, we have examined systemic effects in vaccinated mice that could be related to the induction of acute phase response. The upregulation of gene encoding serum amyloid P component (prototypic mouse acute phase reactant) was detected in the liver and to a lesser degree in the tumor of vaccinated mice at 24 h post-PDT vaccine treatment. A strong upregulation of gene for heat shock protein 70 was found in both the liver and tumor of mice at 4 h after their PDT vaccine treatment. Changes in the expression of genes for glucocorticoid-induced leucine zipper and serum- and glucocorticoid-regulated kinase 1 that are highly responsive to glucocorticoid modulation were uncovered in both the tumor and liver of vaccinated mice. A rise in the levels of serum corticosterone was detected in mice at 24 h after PDT vaccine treatment. The results indicate that a sudden appearance of a large number of PDT vaccine cells elicits host responses for securing their optimized clearance, which in addition to producing seminal acute phase reactants includes the engagement of glucocorticoid hormones. It is becoming increasingly clear that a consummate execution of this process of PDT vaccine cell removal is critical for tumor antigen recognition and the attainment of potent antitumor immune response.
Insights
Photodynamic therapy (PDT) cancer vaccines trigger an acute phase response in mice, involving heat shock proteins and glucocorticoid hormones. This host response is crucial for clearing vaccine cells and generating a potent antitumor immune response.
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- Photodynamic therapy (PDT)-generated cancer vaccines show promise in preclinical and clinical settings.
- Understanding the systemic effects of PDT vaccines is essential for optimizing their efficacy.
Purpose of the Study:
- To investigate the acute phase response and systemic effects in mice vaccinated with a PDT-induced whole-cell autologous cancer vaccine.
- To explore the role of host response mechanisms in PDT vaccine clearance and antitumor immunity.
Main Methods:
- Utilized an SCCVII mouse squamous cell carcinoma model for autologous PDT vaccine generation.
- Analyzed gene expression of acute phase reactants (Serum amyloid P component, Heat shock protein 70) and glucocorticoid-responsive genes in liver and tumor tissues.
- Measured serum corticosterone levels post-vaccination.
Main Results:
- Upregulation of Serum amyloid P component gene in liver and tumor 24 h post-PDT vaccine treatment.
- Significant upregulation of Heat shock protein 70 gene in liver and tumor 4 h post-treatment.
- Altered expression of glucocorticoid-modulated genes (glucocorticoid-induced leucine zipper, serum- and glucocorticoid-regulated kinase 1) observed in both tissues.
- Increased serum corticosterone levels detected 24 h after PDT vaccine administration.
Conclusions:
- PDT vaccine cells induce host responses, including acute phase reactants and glucocorticoid hormones, for optimized clearance.
- Effective clearance of PDT vaccine cells is critical for tumor antigen recognition and potent antitumor immune responses.
- These findings highlight the interplay between host response and vaccine efficacy in PDT-generated cancer vaccines.
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