Abstract: TH-PO0084
Kidney Perspective of a Novel Fusion Protein Immune Agent: Anti-PD1/Mutated IL-15 Fusion Protein
Session Information
- AKI: Pathogenesis and Disease Mechanisms
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 102 AKI: Clinical, Outcomes, and Trials
Authors
- Cintrón-García, Juan J., The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
- Boldt, Christopher, Baylor College of Medicine, Houston, Texas, United States
- Tchakarov, Amanda, The University of Texas Health Science Center at Houston, Houston, Texas, United States
- Workeneh, Biruh, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
Introduction
Approach to cancer treatment through immunoregulatory mechanisms as in Immune Checkpoint Inhibitors(ICI) is quickly revealing promising therapeutic options.ICI gents targeting CTLA-4,PD-1 and PDL-1 are increasingly utilized.However, resistance and relapse remain challenges. IL-15 enhances immune activation, promotes expression of checkpoint molecules (PD-1/PDL-1), and supports NK and CD8+ T cell survival, leading to development of fusion protein like anti-PD1/mutated IL-15.ICI nephrotoxicity has also been well documented however kidney injury as a result of this agent has not been described, to our knowledge.
Case Description
27 yo F, hx of colorectal ca diagnosed 3/2021, relapsed despite multiple lines of treatment.Enrolled in clinical trial 12/2024, started treatment with agent anti PD1/mutated IL-15.Admitted 1/2025 for flu-like symptoms/nausea/vomiting/diarrhea, elevated creatinine.Consulted to Onconephrology for AKI with creatinine(Cr) 7.72 mg/dL and peak 8.89, no hydronephrosis on renal US, not uremic on exam.In addition to prerenal, worsening creatinine despite IV fluids.Urine suggestive of ATI with urine Na 57, Cl 36, concern for ICI nephrotoxicity in the setting of recently started agent.Started prednisone empirically, kidney biopsy done during hospitalization, discharged with Cr 2.33 and return to baseline Cr 0.4-0.6 in 1.5 weeks.
Discussion
ICI-associated nephrotoxicity is typically immune-mediated, with acute interstitial nephritis (AIN) being most common.This fusion agent seeks to concentrate immune effects on PD-1+ tumor-infiltrating lymphocytes, potentially minimizing systemic impact to normal tissue.
Kidney biopsy confirmed interstitial inflammation/tubulointerstitial nephritis and ATI consistent with acute tubular necrosis. Although this adverse effect has been associated with anti PD-1 and other ICIs, to our knowledge, this is the first documented case of kidney injury related to anti-PD1/mutated IL-15. Ongoing surveillance and case accumulation are essential to assess nephrotoxic risk and compare it with traditional ICI agents.