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Updated: May 31, 2026
Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
Induction of effective antitumor response after mucosal bacterial vector mediated DNA vaccination with endogenous
Sarfraz Ahmad1, Garrett Casey, Michelle Cronin
1Leslie C. Quick Jr. Laboratory, Cork Cancer Research Centre, and Department of Surgery, Mercy University Hospital, University College Cork, Cork, Ireland.
Purpose:
The induction of systemic immune responses against antigenic targets that are over expressed by cancer cells represents a powerful therapeutic strategy to target metastatic cancer. We generated specific antitumor immune responses in a murine model of prostate cancer by oral administration of an attenuated strain of Salmonella typhimurium containing a plasmid coding for murine prostate stem cell antigen.
Materials And Methods:
Trafficking of S. typhimurium SL7207 in the initial 10 hours after gavage feeding was determined using a bacterial lux expressing strain and live bioluminescence imaging. For vaccination trials male C57 BL/6 mice were gavage fed SL7207/murine prostate stem cell antigen expressing plasmid or controls twice at 2-week intervals. One week after the last feeding the mice were challenged subcutaneously with TRAMPC1 murine prostate carcinoma cells. Tumor dynamics and animal survival were recorded.
Results:
Clearance of bacterial vector from animals was complete 9 hours after feeding. Delivery of vector transformed with a firefly luciferase reporter plasmid resulted in maximal eukaryotic reporter gene expression in splenocytes 48 hours after feeding. Induction of tumor protective immunity was achieved by feeding the mice murine prostate stem cell antigen expressing plasmid bearing bacteria and greater than 50% of immunized mice remained tumor free. No significant toxicity was observed. Induction of T-helper type 1 immune responses was determined by measuring interferon-γ produced by splenocytes from vaccinated mice. When adoptively transferred to naive animals, splenocytes from vaccinated mice prevented tumor growth in 66% of challenged animals.
Conclusions:
Endogenous prostate cancer antigen gene delivery using a bacterial vector resulted in breaking immune tolerance to murine prostate stem cell antigen and significant retardation of tumor growth.
Insights
Oral administration of attenuated Salmonella typhimurium carrying a prostate stem cell antigen gene induced potent antitumor immunity in a mouse model, leading to significant tumor growth retardation and prolonged survival.
Area of Science:
- Immunology
- Oncology
- Microbiology
Background:
- Systemic immune responses against cancer-specific antigens offer a promising therapeutic avenue for metastatic cancers.
- Prostate stem cell antigen (PSCA) is overexpressed in prostate cancer cells, making it a viable target for immunotherapy.
Purpose of the Study:
- To investigate the efficacy of using an attenuated Salmonella typhimurium strain as a bacterial vector for oral delivery of the murine prostate stem cell antigen (mPSCA) gene.
- To generate specific antitumor immune responses and evaluate therapeutic effects in a murine model of prostate cancer.
Main Methods:
- Salmonella typhimurium SL7207 carrying an mPSCA-expressing plasmid was administered orally to C57 BL/6 mice.
- Mice were challenged with TRAMPC1 prostate carcinoma cells, and tumor dynamics and survival were monitored.
- Immune responses, including interferon-gamma production, were assessed in splenocytes.
Main Results:
- The bacterial vector was cleared within 9 hours post-administration.
- Oral vaccination with the mPSCA-expressing Salmonella strain resulted in over 50% of mice remaining tumor-free.
- Adoptive transfer of splenocytes from vaccinated mice prevented tumor growth in 66% of recipients, indicating robust cellular immunity.
- No significant toxicity was observed.
Conclusions:
- Bacterial vector-mediated delivery of endogenous prostate cancer antigen genes can break immune tolerance.
- This approach leads to significant retardation of tumor growth and establishes protective antitumor immunity.
