SIR 2024
Interventional Oncology
Mohammad Mirza-Aghazadeh-Attari, MD, MPH
Postdoctoral Research Fellow
Johns Hopkins University
Financial relationships: Full list of relationships is listed on the CME information page.
Arun Kamireddy, MD, MBBS
Research fellow
Johns Hopkins University School of Medicine
Financial relationships: Full list of relationships is listed on the CME information page.
Alan J. Kim, BS (he/him/his)
Medical Student
Johns Hopkins University School of Medicine
Financial relationships: Full list of relationships is listed on the CME information page.
Tara Srinivas, MS
Medical Student
Johns Hopkins School of Medicine
Disclosure information not submitted.
Clifford R. Weiss, MD, FSIR
Professor of Radiology and Biomedical Engineering
The Johns Hopkins Hospital
Financial relationships: Full list of relationships is listed on the CME information page.
1-Provide a brief description of Chimeric antigen receptor (CAR) T cells and their expanding role in oncology
2-Revisit the current limitations of systemic CAR-T cell therapy.
3-Describe the critical role of diagnostic and interventional radiologists in administration and follow-up of CAR-T cell therapy, and discuss opportunities for further integration of imaging, minimally invasive procedures and immune-oncology.
Background:
All CAR-T cell therapies approved by the FDA target hematologic malignancies. However recent clinical trials have investigated the role of CAR-T cells in solid tumors, including tumors of the gastrointestinal (GI) system. With the extended application of CAR-T cells in different body organs and tumor environments, the current limitations of systemic CAR-T cell therapy are becoming increasingly evident(1). Interventional Radiologists (IR) are equipped with particular set of skills that may help in overcoming these limitations.
Clinical Findings/Procedure Details:
Three major barriers limit the application of systemically delivered CAR-T cells:
1) Significant variance exists in tumor antigens among different regions of solid tumors, as well as in the dynamic genomic profile of cancerous cells. IRs can play a crucial role in sampling of tissue, as they are well equipped to facilitate extensive tissue sampling from solid tumors. Furthermore, obtaining specimens from the tumor microenvironment (TME) can aid in detection of specific biomarkers that can be targeted for therapy(2).
2) The second barrier is the pharmacodynamics of CAR-T cell delivery to solid tumors. Conventionally, T cells have been delivered using systemic delivery, which is associated with high rates of adverse effects. Experimental studies have shown the efficacy of locoregional delivery of T cells in Mesothelioma (intrapleural injection) and glioblastoma (intraventricular injection)(3). Considering that tumors of the GI system are an emerging target for CAR-T cell therapy, IRs are the most suited clinicians for local delivery of these agents.
3) The TME is hostile towards the immune system, limiting the longevity of T cells in vivo. Studies have shown that locoregional therapies such as ablation or embolization can shift the immune suppressive properties of the TME(4), offering the potential of neoadjuvant local ablation before CAR-T cell therapy.
Conclusion and/or Teaching Points:
IRs are well suited to undertake a leading role in the expansion of CAR-T cell therapy, either by facilitating efficient delivery of cells, quantification of response to treatment or incorporating CAR-T cells into established clinical guidelines.