Related Experiment Video
Updated: Jun 14, 2026
An Orthotopic Model of Serous Ovarian Cancer in Immunocompetent Mice for in vivo Tumor Imaging and Monitoring of Tumor Immune Responses
Published on: November 28, 2010
First-In-Human Trial of Encapsulated Cell-Based Protein Producers for Localized IL-2 in Patients with High-Grade
Helen D Clark1, Samira Aghlara-Fotovat2,3, Jake Schladenhauffen4
1Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center; Houston, Texas, USA.
Background:
Platinum-resistant high-grade serous ovarian carcinomas (HGSOC) are associated with poor therapeutic outcomes. While HGSOC frequently metastasizes to the intraperitoneal (IP) cavity, the success of IP cytokine therapies, such as IL-2, has been hampered by local toxicity and administration difficulties. AVB-001 is a novel IL-2 delivery system consisting of encapsulated, allogeneic cells engineered for constitutive human IL-2 expression.
Methods:
This is a phase I dose-escalation trial of AVB-001 for the treatment of HGSOC (NCT05538624). A single dose of AVB-001 was administered IP laparoscopically, enabling hIL-2 doses from 0.6 to 3.6 μg hIL-2/kg/day. Safety was evaluated using NCI CTCAE v5.0. Efficacy was assessed via RECIST v1.1 criteria.
Findings:
The trial enrolled 14 patients across four dose levels. Three patients (21.4%) experienced grade 3 treatment-related adverse events (TRAEs); no grade 4-5 TRAEs were reported. There was one unconfirmed partial response lasting 29 days (ORR 7.1%). Stable disease was observed in seven patients, with a median duration of 2.57 months (range 2.03-4.23). Pharmacokinetics demonstrated dose-dependent increases in serum IL-2, peaking at 1 day post-implantation. Immunological analyses revealed sustained CD8+ and CD4+ T-cell proliferation without corresponding proliferation in regulatory T cells. Dose-dependent CTLA-4 receptor upregulation was observed on CD8+ and CD4+ T cells, whereas PD-1 and TIM-3, remained unchanged.
Conclusion:
In patients with HGSOC, AVB-001 is safe and effectively activates cytotoxic T cells, supporting further investigation of this locoregional immunotherapy.
Insights
AVB-001, a novel interleukin-2 (IL-2) delivery system, shows promise for treating platinum-resistant high-grade serous ovarian cancer (HGSOC). This locoregional immunotherapy is safe and activates cytotoxic T cells in patients.
Area of Science:
- Oncology
- Immunotherapy
- Drug Delivery Systems
Background:
- Platinum-resistant high-grade serous ovarian carcinomas (HGSOC) present significant therapeutic challenges.
- Intraperitoneal (IP) cytokine therapies, like IL-2, are limited by toxicity and administration issues.
- AVB-001 is a novel encapsulated allogeneic cell system for sustained IL-2 expression.
Purpose of the Study:
- To evaluate the safety and efficacy of AVB-001 in patients with HGSOC.
- To determine the maximum tolerated dose and dose-limiting toxicities of AVB-001.
- To assess the pharmacokinetic and immunologic effects of AVB-001.
Main Methods:
- Phase I, dose-escalation trial of AVB-001 administered IP laparoscopically.
- Dose range: 0.6 to 3.6 μg hIL-2/kg/day.
- Safety assessed by NCI CTCAE v5.0; efficacy by RECIST v1.1.
Main Results:
- 14 patients enrolled across four dose levels; 3 (21.4%) experienced grade 3 TRAEs; no grade 4-5 TRAEs.
- One unconfirmed partial response (7.1%); stable disease in 7 patients (median 2.57 months).
- Dose-dependent serum IL-2 increase; sustained CD8+ and CD4+ T-cell proliferation without Treg increase; CTLA-4 upregulation on T cells.
Conclusions:
- AVB-001 is safe and well-tolerated in HGSOC patients.
- AVB-001 effectively activates cytotoxic T cells in the tumor microenvironment.
- AVB-001 supports further investigation as a locoregional immunotherapy for HGSOC.
