ICAM-1 CAR T-Cell Therapy Shows Promise in Aggressive Thyroid Cancers

Anaplastic thyroid cancer (ATC) and relapsed/refractory poorly differentiated thyroid cancer (PDTC) are aggressive thyroid cancers with limited treatment options and poor prognoses. Standard treatments like surgery, radiation, chemotherapy, and targeted therapies often fail to provide durable responses for these patients. This highlights the urgent need for innovative therapeutic approaches. 

CAR T-cell therapy, which has shown remarkable success in hematological malignancies, is now being explored for solid tumors like ATC and PDTC. A study led by Samer Srour, MB, ChB, MS, focuses on AIC100, a novel third-generation CAR T-cell therapy specifically engineered to target ICAM-1 (Intercellular Adhesion Molecule-1), a protein overexpressed on these thyroid cancer cells and known to play a role in tumor growth and spread. 

Srour, assistant professor, Department of Stem Cell Transplantation, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center explains that AIC100 is designed with several key features to enhance its safety and efficacy. The CAR T-cells are affinity-tuned to selectively bind and kill tumor cells while minimizing harm to healthy tissues. Additionally, AIC100 co-expresses somatostatin receptor 2, allowing clinicians to monitor the CAR T-cells' location and activity within the body using DOTATATE PET scans. This unique tracking mechanism could provide valuable insights into treatment response and potential resistance. 

The phase 1 clinical trial aimed to assess the safety and determine the optimal dose of AIC100 in patients with advanced ATC and PDTC. Early results demonstrated an acceptable safety profile at the initially planned dose levels, with manageable cytokine release syndrome, a common side effect of CAR T-cell therapy. Encouragingly, durable responses, including complete and partial remissions, were observed in some patients, particularly those with ATC, providing a "proof of concept" for this therapeutic strategy in aggressive thyroid cancers. The identification of the recommended phase 2 dose will pave the way for further studies to confirm these findings in a larger patient population and to explore the clinical utility of AIC100 in improving patient outcomes. 

REFERENCE:

Srour S, Lorch J, Zafereo M, et al. ICAM-1 directed chimeric antigen receptor (CAR) T cells (AIC100) in patients with advanced thyroid cancers: Clinical and translational data from the phase 1 dose escalation study. Presented at AACR Annual Meeting 2025; April 25-30, 2025; Chicago, IL. Abstract CT206.