Related Experiment Video
Updated: Jun 6, 2026
Unveiling Therapeutic Opportunities with Melanoma Patient-derived Organoid Models
Published on: September 6, 2024
Modeling Melanoma Immune Surveillance by CAR-T Cells in Human Skin Organoids
Korvell Russell1,2, Anam Adil3, Rohan Shivde4
1Department of Dermatology, Northwestern University, Chicago, IL, USA.
Abstract:
T cell-mediated therapies are major breakthroughs in the treatment of melanoma. However, clinical hurdles in the application of T cell-mediated therapies in melanoma persist and limit their potential. As such, preclinical research efforts remain focused on their development and optimization. Preclinical research techniques include in vivo evaluation with xenograft mouse models, ex vivo patient tumor explant culture, and in vitro tumor spheroids and melanoma/T cell co-cultures. However, these models lack the appropriate tissue context of melanoma skin cancer. Here, we describe a technique for the incorporation of primary T cells and chimeric antigen receptor (CAR)-T cells with melanoma cells in human skin organoids derived from primary epidermal keratinocytes.
Insights
Researchers developed a new preclinical model for melanoma treatment. This human skin organoid model incorporates melanoma cells with T cells, offering better tissue context for therapy development.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- T cell-mediated therapies show promise for melanoma treatment but face clinical application challenges.
- Current preclinical models (xenografts, explants, co-cultures) lack the necessary tissue context for melanoma.
- Optimization of T cell-based melanoma therapies requires improved preclinical research models.
Purpose of the Study:
- To develop an advanced preclinical model for evaluating T cell-mediated therapies in melanoma.
- To create a human skin organoid system that accurately mimics the melanoma tumor microenvironment.
- To facilitate the study of primary T cells and chimeric antigen receptor (CAR)-T cells in conjunction with melanoma cells within a relevant tissue context.
Main Methods:
- Generation of human skin organoids from primary epidermal keratinocytes.
- Incorporation of melanoma cells into the skin organoid structure.
- Co-culture of melanoma cells within the organoid with primary T cells and chimeric antigen receptor (CAR)-T cells.
Main Results:
- Successfully established a human skin organoid model containing melanoma cells.
- Demonstrated the integration and interaction of primary T cells and CAR-T cells within the melanoma-bearing organoid.
- The organoid system provides a more physiologically relevant tissue context compared to traditional models.
Conclusions:
- The developed human skin organoid model offers a novel and improved platform for preclinical evaluation of T cell-based melanoma therapies.
- This model overcomes limitations of existing preclinical systems by providing essential tissue context.
- Further research using this organoid system can accelerate the optimization and clinical translation of advanced melanoma treatments.
