Breakthrough CAR T Cell Therapy Shows Promise for Advanced Thyroid Cancer Patients, AACR Reports

A groundbreaking advance in the treatment of aggressive thyroid cancers has emerged from the laboratories of The University of Texas MD Anderson Cancer Center, offering renewed hope for patients facing these devastating diagnoses. Researchers have unveiled promising early results from a first-in-human Phase I clinical trial of a novel chimeric antigen receptor T cell therapy, designated AIC100, specifically engineered to target the intercellular adhesion molecule 1 (ICAM-1) expressed on certain refractory thyroid tumors. This study marks a pivotal milestone in the quest to extend the benefits of CAR T cell therapies beyond hematologic malignancies and into the notoriously difficult realm of solid tumors.

Thyroid cancers such as anaplastic thyroid cancer (ATC) and poorly differentiated thyroid cancer (PDTC) are characterized by their aggressive nature and poor prognosis, with conventional treatments offering limited survival benefits and an average patient lifespan often measured in months. AIC100’s targeted mechanism seeks to address the critical unmet need in these diseases by leveraging the immune system’s cytotoxic T lymphocytes, reprogrammed to recognize and eradicate ICAM-1 expressing tumor cells. This therapeutic approach not only signifies a novel strategy for thyroid cancers but also expands the potential horizons of CAR T cell technology.

The AIC100 construct represents a third-generation CAR T cell, incorporating enhancements intended to improve efficacy and persistence within the hostile tumor microenvironment of solid cancers. Specifically, AIC100’s CAR molecule binds the ICAM-1 protein, a transmembrane glycoprotein frequently overexpressed in ATC and PDTC cells, facilitating tumor infiltration and cytotoxic activity. Importantly, the CAR T cells co-express somatostatin receptor 2, allowing real-time in vivo tracking using positron emission tomography (PET) imaging, a sophisticated adaptation that enables clinicians to monitor distribution and treatment response non-invasively.

In this multicenter Phase I trial, 24 adult patients with newly diagnosed or relapsed/refractory ATC or PDTC were enrolled, many of whom had exhausted standard-of-care therapies with an average of two prior treatment regimens. The study employed a dose-escalation design exploring three initial dose levels of AIC100 administered after a lymphodepleting chemotherapy regimen, intended to enhance CAR T cell engraftment by reducing host regulatory immune cells. Of these patients, 15 received the investigational therapy, and evaluable data from dose levels two and three revealed encouraging clinical activity.

Specifically, among four ATC patients treated at the higher dose cohorts, the overall objective response rate reached 50%, with one achieving a complete response and another demonstrating a partial response. This level of tumor reduction and durable disease control, sustained up to seven months post-infusion, is unprecedented in this patient population. Moreover, in five PDTC patients, 60% experienced disease stabilization, suggesting both types of thyroid cancer may be amenable to this immunotherapeutic approach.

Safety signals from the trial were favorable, with no dose-limiting toxicities observed at the first three dose levels. Most adverse events comprised mild to moderate cytokine release syndrome (CRS), a common immune activation-related toxicity seen in CAR T therapies, which was manageable and transient. Notably, no cases of immune effector cell-associated neurotoxicity syndrome (ICANS), a frequent and serious complication in CAR T cell treatment, were reported. However, exploration of a fourth, escalated dose revealed the emergence of grade 3 pneumonitis in two patients, underscoring the necessity for careful dose optimization.

The safety profile combined with early efficacy led investigators to select dose level three as the recommended dose for future Phase II trials. These findings provide a compelling proof of concept for the application of CAR T cell therapy in solid tumors, an area historically fraught with challenges due to tumor heterogeneity, immune suppression within the tumor microenvironment, and physical barriers to T cell trafficking.

AIC100’s innovative design, including the somatostatin receptor PET-tracking feature, offers an important tool for understanding CAR T cell kinetics and persistence over time, which are critical parameters linked to long-term therapeutic success. This dual functionality may enable dynamic treatment adjustments and early identification of resistance or relapse, ultimately improving patient outcomes through precision immunotherapy.

Samer Srour, MB ChB, associate professor and principal investigator of the trial, emphasized the transformative potential these results hold. He noted that achieving complete and partial remissions in such an aggressive clinical setting is both a validation of the therapeutic strategy and an impetus for further development. The prospect of durable remissions could shift the current therapeutic landscape and significantly extend survival for patients afflicted with these lethal thyroid cancer subtypes.

This Phase I study was funded by AffyImmune Therapeutics, reflecting a productive academic-industry collaboration crucial for advancing cutting-edge immuno-oncology interventions. As the team prepares for larger-scale investigations, the oncology community eagerly anticipates more robust data on efficacy and long-term safety that could pave the way for regulatory approval and expanded clinical use.

In summary, the promising safety and efficacy profile of AIC100 in this early clinical evaluation signals a new frontier in the treatment of solid tumors, highlighting the potential for tailored CAR T cell therapies to overcome previous barriers and improve outcomes in hard-to-treat thyroid cancers. Further developments in this line of research could bring a much-needed paradigm shift, transforming fatal diagnoses into manageable chronic conditions or potentially curable diseases.

• https://www.mdanderson.org/treatment-options/car-t-cell-therapy.html
• https://www.mdanderson.org/cancer-types/thyroid-cancer.html
• https://faculty.mdanderson.org/profiles/samer_srour.html
• https://www.abstractsonline.com/pp8/#!/20273/presentation/10430
• https://www.aacr.org/meeting/aacr-annual-meeting-2025/
• https://MDAnderson.org/AACR
  Image Credits: The University of Texas MD Anderson Cancer Center
  Keywords: Cancer treatments, Cell therapies, Thyroid cancer, Cancer patients, T cell responses, Clinical trials, T lymphocytes, Thyroid diseases, Gene targeting, Cellular proteins, Solid tumors, Target proteins, Cancer research, Cancer relapse, Neurological disorders, Tumor cells, Disease control