CAR T Therapy Targeting ICAM-1 Eliminates Advanced Human Thyroid Tumors

Area of Science:

• Oncology
• Immunotherapy
• Molecular Biology

Background:

• Poorly differentiated and anaplastic thyroid cancer (ATC) are aggressive malignancies with limited therapeutic options.
• Increased intercellular adhesion molecule-1 (ICAM-1) expression is observed in various cancers, including papillary thyroid cancer (PTC) and ATC.
• ICAM-1 presents a potential therapeutic target for aggressive cancers.

Purpose of the Study:

• To develop and evaluate a third-generation chimeric antigen receptor (CAR) T-cell therapy targeting ICAM-1 for aggressive thyroid cancers.
• To investigate the efficacy and specificity of ICAM-1 CAR T cells against both established cell lines and patient-derived ATC tumors.
• To assess the potential of ICAM-1 CAR T-cell therapy in preclinical models of metastatic ATC.

Main Methods:

• Development of a third-generation CAR T-cell construct targeting ICAM-1.
• In vitro assessment of ICAM-1 CAR T-cell cytotoxicity against various malignant and nonmalignant cell lines.
• In vivo evaluation of therapeutic efficacy in mouse models of systemic ATC, including those derived from patient tumors.
• Analysis of ICAM-1 expression modulation upon CAR T-cell treatment.

Main Results:

• ICAM-1 CAR T cells demonstrated specific and potent killing of PTC and ATC cell lines in vitro.
• Heterogeneous ICAM-1 expression in ATC cell lines was overcome, as T-cell treatment induced targetable ICAM-1 levels.
• A single administration of ICAM-1 CAR T cells led to significant tumor reduction, long-term remission, and improved survival in mice with systemic ATC.
• Patient-derived ATC cells, which overexpressed ICAM-1, were effectively eliminated by autologous ICAM-1 CAR T cells in vitro and in vivo.

Conclusions:

• This study presents the first demonstration of CAR T-cell therapy targeting ICAM-1 for metastatic thyroid cancer and advanced ATC.
• ICAM-1 CAR T-cell therapy exhibits significant therapeutic efficacy and survival benefits in preclinical models of aggressive thyroid cancer.
• These findings support the potential of ICAM-1-targeted CAR T-cell therapy as a novel treatment modality for lethal thyroid malignancies.