Zainab Obaidi

Zainab Obaidi is an Assistant Professor at the University of Chicago, specializing in nephrology with a particular interest in glomerular diseases and thrombotic microangiopathies. She completed the Master of Education for Healthcare Professionals (MEHP) at Johns Hopkins, focusing on medical education among medical students, residents, and fellows. As a member of the Glomerular Clinic team at UChicago, she delivers comprehensive patient care and engages in research to advance the understanding of these conditions.

The remaining competitors, our Left and Right Kidneys:

Team CAR-T for Autoimmune Diseases vs Team MCD Diagnosis and Pathogenesis

For this year’s epic showdown in NephMadness, we introduce the one and only CAR-T—First of Its Name, Conqueror of B Cells, and Guardian of Nephrons! If you’ve been following the excitement, you know that CAR-T therapy has made waves in oncology and is now stepping into the spotlight of nephrology. The concept of collecting a patient’s T cells, genetically modifying them using a viral vector to produce chimeric antigens (CARS), and then reinfusing these engineered cells back into the patient is nothing short of groundbreaking. If that doesn’t spark your interest, let’s dive into why CAR-T therapy is poised to become the frontrunner in NephMadness 2025!

Round one: Loop the loop with lupus nephritis.

Refractory lupus nephritis poses a real challenge, especially when self-reactive B cells hide deep within lymphatic tissue and evade our go-to B cell-depleting therapies like Rituximab. A recent study from Germany revisited CD19-directed CAR-T therapy to eight patients with refractory lupus nephritis. The results were promising, with sustained remission lasting up to two years after treatment despite reconstitution of naïve B cells. This highlights the promising potential of deep B cell depletion for managing refractory autoimmune diseases like lupus nephritis.

Round two: Dialysis who?

CAR-T has been a game changer for refractory multiple myeloma and lymphoma patients, even when on dialysis. This calls for a multidisciplinary approach with the nephrologist at the center, effectively dialyzing patients receiving CAR-T therapy while limiting the toxicities of the lymphodepleting agents given and facilitating appropriate drug distribution prior to CAR-T therapy.

Round Three: What’s on the horizon?

CAR-T therapy is unique as it is the cornerstone of precision medicine which offers tailored treatment for patients with malignancy or autoimmune disease. In 2023, CAR-T therapies targeting CD38 (a cell surface glycoprotein found in tumor cells) were developed by integrating CD38-specific CARs into the CD38 gene locus, creating the CAR-T and CAR-NK cells now used to treat multiple myeloma and leukemias.

Future directions of CAR-T therapies include exploration of different antigen targets, with ongoing studies to investigate next-generation CAR-T options for leukemia patients designed to prevent relapses. These innovative approaches feature “dual antigen CAR-T” (a single vector encoding two CARs) or “Multi CAR-T” therapies.  Additionally, researchers are enhancing treatment outcomes by employing gene editing techniques to knock out PD-1 or CTLA-4, facilitating a more sustained immune response against cancer, or using immune checkpoint inhibitors (ICIs) alongside CAR-T therapy to overcome the tumor’s immunosuppressive environment.

Additionally, efforts to curb costs and improve availability include the development of “off the shelf” or allogenic CAR-T cells donated by healthy donors, which can be readily used and save time in treatment.

The verdict:

CAR-T—The First of Its Name—holds great promise and has a chance to win this year in NephMadness 2025! It represents a significant advancement in treating kidney diseases and sparing patients from the burdens of dialysis. Its innovative approach to refractory conditions like lupus nephritis, along with its effectiveness in onconephrology patients, including those undergoing dialysis, underscores its transformative potential. By opening new avenues for treatment and personalizing patient care, we are closer than ever to revolutionizing nephrology. Let’s champion CAR-T for Autoimmune Diseases as the future of our field!

Copyright: sirtravelalot / Shutterstock

– Guest Post written by Zainab Obaidi

As with all content on the AJKD Blog, the opinions expressed are those of the author of each post, and are not necessarily shared or endorsed by the AJKD Blog, AJKD, the National Kidney Foundation, Elsevier, or any other entity unless explicitly stated.

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