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[Adoptive Cell Therapy with Immune Checkpoint Blockade]
1Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University.
Abstract:
Cancer immunotherapy are taking a leading role of cancer therapy due to the development of the immune checkpoint blockade. To date, however, only about 20% of patients have clinical responses and the cancer-specific T cells in cancer site are required to obtain beneficial effects. There has been an innovative development in the field of adoptive cell therapy, especially receptor gene-modified T cells in recent years. The effector cells mostly express PD-1, therefore the cytotoxic reactivity of the effector cells are inhibited by PD-L1. The combination of the adoptive cell therapy and the immune checkpoint blockade is expected to enhance efficacy. On the other hand, the immune-related adverse events may also be enhanced, therefore, it is needed to develop the combination therapy carefully, improving the cancer antigen-specificity or dealing with the cytokine release syndrome.
Insights
Cancer immunotherapy using immune checkpoint blockade shows promise but benefits only 20% of patients. Combining this with adoptive cell therapy may improve outcomes, but requires careful management of side effects.
Area of Science:
- Oncology
- Immunology
- Cell Therapy
Background:
- Immune checkpoint blockade is a leading cancer therapy, but clinical responses are limited.
- Effective cancer immunotherapy requires cancer-specific T cells at the tumor site.
- Adoptive cell therapy, particularly engineered T cells, is an emerging treatment modality.
Purpose of the Study:
- To explore the potential of combining adoptive cell therapy with immune checkpoint blockade for enhanced cancer treatment efficacy.
- To address the challenges associated with combining these two immunotherapeutic approaches.
Main Methods:
- Investigating the role of PD-1 expression on effector T cells in adoptive cell therapy.
- Analyzing the inhibitory effect of PD-L1 on T cell cytotoxic activity.
- Considering strategies for combining engineered T cell therapy with immune checkpoint inhibitors.
Main Results:
- Effector cells in adoptive cell therapy often express PD-1, making them susceptible to PD-L1 mediated inhibition.
- Combining adoptive cell therapy with immune checkpoint blockade is hypothesized to increase treatment effectiveness.
- Potential for enhanced immune-related adverse events necessitates careful therapeutic development.
Conclusions:
- Combination therapy holds promise for improving cancer immunotherapy outcomes.
- Careful development is crucial to mitigate risks such as cytokine release syndrome.
- Enhancing cancer antigen-specificity is key for successful combination strategies.
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