Related Experiment Video
Updated: May 7, 2026
A Nonviral Approach to Generate Transient Chimeric Antigen Receptor T Cells Using mRNA for Cancer Immunotherapy
Published on: February 21, 2025
Pan-cancer analysis identifies CD155 as a promising target for CAR-T cell therapy
Xiaohong Liu1, Yue Sun1, Boxu Lin1
1Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Background:
Chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable success in treating hematologic malignancies. However, its efficacy against solid tumors remains limited. One of the major challenges is the lack of specific tumor antigens. Therefore, the exploration and rational selection of novel tumor targets is urgently needed. In this study, we investigate the therapeutic potential of targeting CD155 in cancer by CAR-T cells.
Methods:
The expression of CD155 was analyzed across various cancer types using data from The Cancer Genome Atlas (TCGA) and validated by tissue microarray analysis. The impact of CD155 on T cell mediated cytotoxicity was analyzed using CD155 over-expression or knockout tumor cells. Subsequently, second-generation CAR-T cells were constructed using either the extracellular domain (ECD) of TIGIT or an anti-CD155 scFv to evaluate their anti-tumor efficacy both in vitro and in vivo.
Results:
We demonstrated that CD155 is specifically overexpressed across various cancer types and that its high expression is strongly associated with poor prognosis, as revealed by data from TCGA. Consistently, CD155 is significantly upregulated in clinical tumor tissues and in numerous cancer cell lines, while it is rarely expressed in normal tissues. Furthermore, CD155 expression is also significantly increased in granulocytes derived from cancer patients compared to those from healthy donors. Functionally, high CD155 expression significantly inhibits the release of cytotoxic factors from T cells, thereby functioning as an immune checkpoint that mediates tumor immune evasion. After comparison, the scFv based anti-CD155 CAR-T cells demonstrated stronger anti-tumor activity than ECD of TIGIT based CAR-T cells. Moreover, the scFv based CAR-T cells exhibited effective anti-tumor activity against multiple CD155+ solid and hematologic tumors both in vitro and in different xenograft mouse models.
Conclusions:
Our study demonstrates that CD155 is selectively expressed in cancer cells while being rarely detected in normal tissues, and may serve as a promising pan-cancer target for CAR-T therapy. Targeting CD155 with CAR-T cells provides an effective approach to treating both solid and hematologic malignancies.
Insights
Targeting CD155 with chimeric antigen receptor T (CAR-T) cells shows promise for treating various cancers. This approach effectively targets CD155-expressing solid tumors and hematologic malignancies, offering a new therapeutic avenue.
Area of Science:
- Immunology
- Oncology
- Cell Therapy
Background:
- Chimeric antigen receptor T (CAR-T) cell therapy is effective against blood cancers but limited against solid tumors due to a lack of specific targets.
- Identifying novel tumor antigens is crucial for expanding CAR-T efficacy.
- This study investigates CD155 as a potential target for CAR-T therapy in cancer.
Purpose of the Study:
- To evaluate the expression of CD155 in various cancer types.
- To assess the therapeutic potential of targeting CD155 using CAR-T cells.
- To compare the efficacy of different CAR constructs targeting CD155.
Main Methods:
- CD155 expression analysis using The Cancer Genome Atlas (TCGA) and tissue microarrays.
- Functional assays assessing T cell cytotoxicity against CD155 modified tumor cells.
- Construction and in vitro/in vivo evaluation of second-generation CAR-T cells targeting CD155 via scFv or TIGIT ECD.
Main Results:
- CD155 is overexpressed in multiple cancer types, associated with poor prognosis, and rarely found in normal tissues.
- High CD155 expression inhibits T cell cytotoxicity, acting as an immune checkpoint.
- Anti-CD155 scFv CAR-T cells demonstrated superior anti-tumor activity compared to TIGIT ECD CAR-T cells in vitro and in vivo models.
Conclusions:
- CD155 is a selectively expressed pan-cancer target with potential for CAR-T therapy.
- Targeting CD155 with CAR-T cells offers an effective strategy for treating both solid and hematologic malignancies.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:27Tumor Immunotherapy