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Updated: Jan 24, 2026
Experimental Metastasis and CTL Adoptive Transfer Immunotherapy Mouse Model
Published on: November 26, 2010
An effective mouse model for adoptive cancer immunotherapy targeting neoantigens
Ken-Ichi Hanada1,2, Zhiya Yu1,2, Gabrielle R Chappell1,2,3
1Surgery Branch, National Cancer Institute (NCI), NIH, Bethesda, Maryland, USA.
Abstract:
The adoptive cell transfer (ACT) of T cells targeting mutated neoantigens can cause objective responses in varieties of metastatic cancers, but the development of new T cell-based treatments relies on accurate animal models. To investigate the therapeutic effect of targeting a neoantigen with ACT, we used T cells from pmel-1 T cell receptor-transgenic mice, known to recognize a WT peptide, gp100, and a mutated version of the peptide that has higher avidity. We gene-engineered B16 cells to express the WT or mutated gp100 epitopes and found that pmel-1-specific T cells targeting a neoantigen tumor target augmented recognition as measured by IFN-γ production. Neoantigen expression by B16 also enhanced the capacity of pmel-1 T cells to trigger the complete and durable regression of large, established, vascularized tumor and required less lymphodepleting conditioning. Targeting neoantigen uncovered the possibility of using enforced expression of the IL-2Rα chain (CD25) in mutation-reactive CD8+ T cells to improve their antitumor functionality. These data reveal that targeting of "mutated-self" neoantigens may lead to improved efficacy and reduced toxicities of T cell-based cellular immunotherapies for patients with cancer.
Insights
Targeting cancer neoantigens with adoptive cell transfer (ACT) using engineered T cells shows enhanced anti-tumor activity. This approach improves therapeutic efficacy and reduces toxicities in preclinical cancer models.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Adoptive cell transfer (ACT) shows promise for metastatic cancers by targeting mutated neoantigens.
- Accurate animal models are crucial for developing novel T cell-based cancer therapies.
Purpose of the Study:
- To investigate the therapeutic potential of targeting a specific neoantigen using ACT.
- To evaluate the efficacy of T cells recognizing a mutated neoantigen compared to a wild-type peptide.
Main Methods:
- Utilized pmel-1 T cells from transgenic mice recognizing gp100 peptide variants.
- Gene-engineered B16 melanoma cells to express wild-type or mutated gp100 epitopes.
- Assessed T cell recognition via IFN-γ production and tumor regression in vivo.
Main Results:
- T cells targeting the neoantigen demonstrated augmented recognition and IFN-γ production.
- Neoantigen expression led to complete and durable regression of established tumors.
- Targeting neoantigens enhanced T cell functionality and reduced the need for lymphodepleting conditioning.
Conclusions:
- Targeting
- mutated-self
- neoantigens with ACT can improve anti-tumor efficacy.
- This strategy may enhance the functionality of CD8+ T cells, potentially via CD25 expression.
- Neoantigen-targeted ACT offers a promising avenue for more effective and less toxic cancer immunotherapy.
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