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Updated: Nov 26, 2025
Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
Systemic and intravesical adoptive cell therapy of tumor-reactive T cells can decrease bladder tumor growth in vivo
Brittany L Bunch1, Jennifer Morse1, Sarah Asby1
1Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
Background:
The therapeutic armamentarium of bladder cancer has been recently enriched with the introduction of new therapies including immune checkpoint inhibitors, receptor tyrosine kinase inhibitors and antibody drug conjugates, however treatment responses and duration of responses are still less than expected. Adoptive cellular therapy (ACT) using tumor-infiltrating lymphocytes (TILs) has potential to treat bladder cancer, as previously demonstrated by successful expansion of tumor reactive T cells from human bladder tumors.
Methods:
A model system using OT-I T cells and an ovalbumin expressing MB49 tumor cell line (MB49OVA) was developed to study ACT in bladder cancer. Systemic ACT-treated mice were given T cells intravenously after lymphodepleting chemotherapy and followed by interleukin (IL)-2 administration. Intravesical ACT treated mice were given T cells directly into the bladder, without chemotherapy or IL-2. TILs were isolated from MB49 orthotopic tumors and expanded ex vivo in IL-2. Immune cell infiltrates were analyzed by flow cytometry. T cell infiltration was studied using a CXCR3 blocking antibody.
Results:
Systemic ACT-treated mice had a decrease in tumor growth, increase in T cell infiltration and long-term immune protection compared with control-treated mice. OT-I T cells delivered intravesically were able to control tumor growth without lymphodepleting chemotherapy or IL-2 in MB49OVA orthotopic tumors. Intravesical delivery of TIL expanded from MB49 tumors was also able to decrease tumor growth in mice with MB49 orthotopic tumors. Blocking CXCR3 on OT-I T cells prior to intravesical delivery decreased T cell infiltration into the tumor and prevented the control of tumor growth.
Conclusions:
This study demonstrates how TIL therapy can be used in treating different stages of bladder cancer.
Insights
Adoptive cellular therapy (ACT) using tumor-infiltrating lymphocytes (TILs) shows promise for bladder cancer treatment. Intravesical TIL therapy effectively controlled tumor growth in mice, offering a new therapeutic avenue.
Area of Science:
- Oncology
- Immunology
- Cell Therapy
Background:
- Bladder cancer therapies, including immune checkpoint inhibitors and antibody drug conjugates, show limited response duration.
- Adoptive cellular therapy (ACT) using tumor-infiltrating lymphocytes (TILs) presents a potential treatment strategy for bladder cancer.
- Successful expansion of tumor-reactive T cells from human bladder tumors supports TIL therapy's potential.
Purpose of the Study:
- To investigate the efficacy of ACT with TILs in a preclinical bladder cancer model.
- To compare systemic versus intravesical delivery of TILs for bladder cancer treatment.
- To elucidate the role of CXCR3 in TIL-mediated anti-tumor responses.
Main Methods:
- Developed a model using OT-I T cells and MB49OVA tumor cells for ACT studies.
- Administered systemic ACT intravenously post-chemotherapy with IL-2, and intravesical ACT directly into the bladder without chemotherapy or IL-2.
- Isolated and expanded TILs from MB49 tumors ex vivo, analyzed immune infiltrates via flow cytometry, and blocked CXCR3 to study T cell infiltration.
Main Results:
- Systemic ACT reduced tumor growth, increased T cell infiltration, and provided long-term immunity.
- Intravesical ACT controlled tumor growth in MB49OVA tumors without chemotherapy or IL-2.
- Intravesical delivery of expanded TILs also decreased tumor growth in MB49 tumors.
- Blocking CXCR3 on T cells reduced tumor infiltration and impaired tumor growth control.
Conclusions:
- TIL therapy demonstrates potential for treating various stages of bladder cancer.
- Intravesical delivery of TILs is an effective strategy for bladder cancer treatment.
- CXCR3 plays a crucial role in TIL trafficking and anti-tumor efficacy.
