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Updated: May 28, 2026
A Human Peripheral Blood Mononuclear Cell (PBMC) Engrafted Humanized Xenograft Model for Translational Immuno-oncology (I-O) Research
Published on: August 15, 2019
PiggyBac-Engineered Membrane-Bound IL7 TILs Combined with Anti-PD-1 Antibody Demonstrates Efficacy in Recurrent
Jing Guo1, Yuliang Wu2, Wei Huang3
1Department of Obstetrics and Gynecology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Purpose:
Recurrent ovarian cancer (rOC) remains an unmet need. This first-in-human phase I trial evaluated GC203, an autologous tumor-infiltrating lymphocyte (TIL) product genetically modified via piggyBac transposon to overcome the immunosuppressive tumor microenvironment.
Patients And Methods:
A cohort of 18 patients with rOC who were heavily pretreated (median, 3.5 prior lines of therapy) underwent lymphodepletion with cyclophosphamide and hydroxychloroquine, followed by GC203 infusion. The primary endpoints were safety and tolerability. Secondary endpoints, assessed in the full analysis set using RECIST 1.1 guidelines, encompassed objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Exploratory analyses included the Morisita overlap index (MOI) to quantify T-cell receptor repertoire similarity between infused TILs and circulating T cells.
Results:
The GC203 regimen demonstrated a favorable safety profile. Treatment-related adverse events were primarily hematologic, with grade ≥ 3 lymphopenia and neutropenia each occurring in 57% of patients. All proved to be transient with a median resolution of 7 days. The regimen achieved an unconfirmed ORR of 33.3% (6/18 patients) alongside a disease control rate of 83.3%. Survival analyses revealed a median PFS of 7.2 months [95% confidence interval (CI), 1-13.4] and a median OS of 17.1 months (95% CI, 9.5-24.7). A key exploratory analysis identified the MOI as a significant predictor of treatment response, achieving an area under the curve of 0.79.
Conclusions:
The GC203 regimen, combining piggyBac membrane-bound IL7 autologous TILs with anti-PD-1 antibody, demonstrates favorable safety and promising efficacy in heavily pretreated patients with rOC, which supports its further development in this high-need population.
Insights
GC203, a novel therapy using genetically modified tumor-infiltrating lymphocytes (TILs), shows promise for recurrent ovarian cancer (rOC). This phase 1 trial indicates favorable safety and encouraging efficacy, supporting further development.
Area of Science:
- Oncology
- Immunotherapy
- Cellular Therapy
Background:
- Recurrent ovarian cancer (rOC) presents a significant unmet medical need.
- Existing treatments for heavily pretreated rOC have limited efficacy.
- The tumor microenvironment (TME) in rOC is often immunosuppressive, hindering anti-tumor immune responses.
Purpose of the Study:
- To evaluate the safety and tolerability of GC203, an autologous tumor-infiltrating lymphocyte (TIL) product genetically modified with a piggyBac transposon.
- To assess the preliminary efficacy of GC203 in patients with recurrent ovarian cancer.
- To explore potential predictive biomarkers of treatment response.
Main Methods:
- A first-in-human, phase 1 trial involving 18 heavily pretreated rOC patients.
- Patients received lymphodepletion followed by GC203 infusion.
- Safety, tolerability, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were assessed. Exploratory analysis included the Morisita Overlap Index (MOI).
Main Results:
- The GC203 regimen demonstrated a favorable safety profile with manageable, transient hematological toxicities.
- An unconfirmed ORR of 33.3% and a disease control rate (DCR) of 83.3% were observed.
- Median PFS was 7.2 months and median OS was 17.1 months. MOI emerged as a predictor of response (AUC=0.79).
Conclusions:
- GC203, an autologous TIL therapy enhanced with piggyBac-mbIL-7 and combined with anti-PD-1 antibody, shows promising safety and efficacy in recurrent ovarian cancer.
- The favorable safety profile and encouraging efficacy support further clinical development of GC203 for rOC.
- The Morisita Overlap Index (MOI) may serve as a predictive biomarker for treatment response in this setting.
