Generating CAR T cells from tumor-infiltrating lymphocytes

Area of Science:

• Immunology
• Oncology
• Cell Therapy

Background:

• Tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T-cell therapies show promise but limited efficacy in melanoma treatment.
• Metastatic melanoma cells often express the Her2 antigen, presenting a potential therapeutic target.

Purpose of the Study:

• To explore the efficacy of dual-specific T cells engineered from melanoma patient TILs with a Her2-specific CAR.
• To evaluate the anti-tumor potential of these modified T cells in preclinical models.

Main Methods:

• Melanoma patient TILs were transduced with a Her2-specific CAR to create CAR-TILs.
• CAR-TILs were co-cultured with Her2-expressing melanoma cell lines, including autologous lines.
• An in vivo study was conducted using NSG mice treated with CAR-TILs via adoptive cell therapy.

Main Results:

• CAR-TILs produced significantly higher amounts of interferon (IFN) compared to parental TILs when co-cultured with Her2-expressing tumor cells.
• While CAR expression did not consistently increase TIL cytotoxicity, adoptive cell therapy with CAR-TILs led to tumor shrinkage in NSG mice.
• Metastatic melanoma cells in the study's biobank constitutively expressed the Her2 antigen.

Conclusions:

• Engineered CAR-TILs demonstrate potential for melanoma treatment by enhancing anti-tumor immune responses and reducing tumor burden in vivo.
• Limitations such as limited proliferative potential and a terminally differentiated phenotype of transduced TILs require further investigation before clinical translation.
• Targeting Her2-expressing melanoma with CAR-TILs represents a promising avenue for novel cancer immunotherapy strategies.