TY - JOUR
T1 - Intraperitoneal infusion of stem cell-derived natural killer cells in recurrent epithelial ovarian cancer patients
T2 - Results of the phase 1 INTRO-01 trial
AU - Evert, Janneke S.Hoogstad van
AU - de Jonge, Paul K.J.D.
AU - Zusterzeel, Petra L.M.
AU - Hobo, Willemijn
AU - van der Waart, Anniek B.
AU - Fredrix, Hanny
AU - Janssen, Lisanne
AU - Wuts, Maud
AU - Bosmans, Lynn
AU - Spijkers, Ellen
AU - Djojoatmo, Merlize
AU - Rodriguez, Veronica Castaño
AU - de Goede, Anna L.
AU - van der Reijden, Bert
AU - van der Meer, Arnold
AU - Schaap, Nicolaas
AU - Bekkers, Ruud
AU - Jansen, Joop H.
AU - Ottevanger, Nelleke
AU - Dolstra, Harry
N1 - Funding Information:
This work is supported by a research grant of the Dutch Cancer Society 10100. We would like to express our sincere gratitude to all the patients, their families, and the staff from all the units that participated in this study. A special thanks goes to the invaluable colleagues of the trial bureau from the Department of Medical Oncology and Radboud trial center (Radboudumc) for their invaluable support with trial data and sampling during the trial. We also extend our appreciation to hospital pharmacist Janine van der Linden and Nienke de Haas and other colleagues from the Department of Pharmacy, Pharmacology and Toxicology (Radboudumc) for support in GMP manufacturing and QP-release of the clinical batches of RNK001 product.
Funding Information:
This work was supported by a Dutch Cancer Society grant 10100.
Publisher Copyright:
© 2025 The Authors
PY - 2026/1/1
Y1 - 2026/1/1
N2 - Introduction: Epithelial ovarian cancer (EOC) patients exhibit a poor 5-year overall survival rate of approximately 40 %, underscoring the urgent need for innovative therapies. Allogeneic natural killer (NK) cell therapy presents a promising and safe therapeutic option, given its ability to discriminate between normal and malignant cells with potent cytotoxic effects against malignant cells. Methods: We present the first-in-human study exploiting the safety of the NK cell product designated RNK001, derived ex vivo from umbilical cord blood-derived hematopoietic stem and progenitor cells. This phase 1 INTRO-01 trial (NCT03539406) was initiated to assess the feasibility, safety, and toxicity of intraperitoneal (IP) infusion of RNK001 in EOC patients exhibiting elevated CA125 levels at the second recurrence. RNK001 infusion was supported by IP IL-2 in six patients, and was preceded in one patient by lymphodepleting chemotherapy with cyclophosphamide/fludarabine. Results: RNK001 consisted of 1.2 to 3.0 × 109 highly activated CD56+CD3- NK cells and was well tolerated, with neither evidence of graft-versus-host disease nor cytokine release syndrome. One patient experienced a grade 3 transient elevation in liver enzymes, another patient exhibited grade 3 ileus caused by disease progression. Notably, five out seven patients demonstrated a reduction in CA125 serum levels of 20–53 % at 14 days post-infusion. Furthermore, one patient achieved a clinical and biochemical response with radiological stable disease and a progression-free survival of 9 months. Conclusion: These findings suggest that intraperitoneal RNK001-based immunotherapy can be safely administered to recurrent EOC patients without inducing severe toxicity, while clinical and biochemical responses warrant further development.
AB - Introduction: Epithelial ovarian cancer (EOC) patients exhibit a poor 5-year overall survival rate of approximately 40 %, underscoring the urgent need for innovative therapies. Allogeneic natural killer (NK) cell therapy presents a promising and safe therapeutic option, given its ability to discriminate between normal and malignant cells with potent cytotoxic effects against malignant cells. Methods: We present the first-in-human study exploiting the safety of the NK cell product designated RNK001, derived ex vivo from umbilical cord blood-derived hematopoietic stem and progenitor cells. This phase 1 INTRO-01 trial (NCT03539406) was initiated to assess the feasibility, safety, and toxicity of intraperitoneal (IP) infusion of RNK001 in EOC patients exhibiting elevated CA125 levels at the second recurrence. RNK001 infusion was supported by IP IL-2 in six patients, and was preceded in one patient by lymphodepleting chemotherapy with cyclophosphamide/fludarabine. Results: RNK001 consisted of 1.2 to 3.0 × 109 highly activated CD56+CD3- NK cells and was well tolerated, with neither evidence of graft-versus-host disease nor cytokine release syndrome. One patient experienced a grade 3 transient elevation in liver enzymes, another patient exhibited grade 3 ileus caused by disease progression. Notably, five out seven patients demonstrated a reduction in CA125 serum levels of 20–53 % at 14 days post-infusion. Furthermore, one patient achieved a clinical and biochemical response with radiological stable disease and a progression-free survival of 9 months. Conclusion: These findings suggest that intraperitoneal RNK001-based immunotherapy can be safely administered to recurrent EOC patients without inducing severe toxicity, while clinical and biochemical responses warrant further development.
KW - Adoptive cell therapy
KW - Clinical trial
KW - Epithelial ovarian cancer
KW - Intraperitoneal therapy
KW - Natural killer (NK) cells
U2 - 10.1016/j.ygyno.2025.11.006
DO - 10.1016/j.ygyno.2025.11.006
M3 - Article
SN - 0090-8258
VL - 204
SP - 91
EP - 99
JO - Gynecologic Oncology
JF - Gynecologic Oncology
ER -