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Generation of Prostate Cancer Patient Derived Xenograft Models from Circulating Tumor Cells
Published on: October 20, 2015
Adoptive cell therapy of prostate cancer using female mice-derived T cells that react with prostate antigens
Huanfa Yi1, Xiaofei Yu, Chunqing Guo
1Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA.
Abstract:
In this study, we report a novel treatment strategy that could potentially be used to improve efficacy of adoptive cell therapy for patients with prostate cancer. We show that female C57BL/6 mice are able to effectively reject two syngeneic prostate tumors (TRAMP-C2 and RM1) in a T cell-dependent manner. The protective antitumor immunity appears to primarily involve T cell responses reactive against general prostate tumor/tissue antigens, rather than simply to male-specific H-Y antigen. For the first time we show that adoptive transfer of lymphocytes from TRAMP-C2-primed or naïve female mice effectively control prostate tumor growth in male mice, when combined with host pre-conditioning (i.e., non-myeloablative lymphodepletion) and IL-2 administration. No pathological autoimmune response was observed in the treated tumor-bearing male mice. Our studies provide new insights regarding the immune-mediated recognition of male-specific tissue, such as the prostate, and may offer new immunotherapy treatment strategies for advanced prostate cancer.
Insights
This study shows adoptive cell therapy can control prostate tumor growth in mice. Combining T cells with lymphodepletion and IL-2 offers a potential new immunotherapy strategy for advanced prostate cancer.
Area of Science:
- Immunology
- Oncology
- Urology
Background:
- Prostate cancer remains a significant health concern, necessitating novel therapeutic approaches.
- Adoptive cell therapy (ACT) shows promise but requires optimization for efficacy.
- Understanding immune responses to prostate tumors is crucial for developing effective immunotherapies.
Purpose of the Study:
- To investigate a novel treatment strategy to enhance ACT efficacy for prostate cancer.
- To determine the role of T cell responses in rejecting prostate tumors.
- To evaluate the potential of adoptive lymphocyte transfer combined with pre-conditioning and IL-2 for controlling prostate tumor growth.
Main Methods:
- Utilized female C57BL/6 mice to study rejection of syngeneic TRAMP-C2 and RM1 prostate tumors.
- Administered adoptive transfer of lymphocytes from primed or naive female mice to tumor-bearing male mice.
- Implemented host pre-conditioning with non-myeloablative lymphodepletion and IL-2 administration.
Main Results:
- Female mice effectively rejected prostate tumors in a T cell-dependent manner.
- Antitumor immunity involved responses to general prostate antigens, not solely H-Y antigen.
- Adoptive cell transfer, combined with lymphodepletion and IL-2, controlled tumor growth in male mice without inducing autoimmune pathology.
Conclusions:
- Prostate tumor rejection is mediated by T cells recognizing general prostate antigens.
- This novel combination therapy shows potential for treating advanced prostate cancer.
- The strategy warrants further investigation as a new immunotherapy for prostate cancer.

