Phase I/II trial of gene therapy with autologous tumor cells modified with tag7/PGRP-S gene in patients with disseminated solid tumors
Open Access
- 1 January 2005
- journal article
- clinical trial
- Published by Elsevier BV in Annals Of Oncology
- Vol. 16 (1), 162-168
- https://doi.org/10.1093/annonc/mdi028
Abstract
Background: The use of genetically modified autologous tumor cells appears to be a promising approach for cancer therapy. A phase I/II trial was undertaken to define the feasibility, safety and antitumor effects of the autologous vaccine prepared by transferring tag7/PGRP-S gene into malignant melanoma and renal cell carcinoma cells. Patients and methods: Twenty-one patients (17 with disseminated malignant melanoma and four with metastatic renal cell carcinoma) were enrolled in this study. Cytoreduction was performed in all cases prior to therapy. Autologous tumor cells were transfected with the tag7/PGRP-S gene, irradiated and injected intradermally every 3 weeks. Results: Vaccinations were well tolerated by all patients, without clinically significant signs of toxicity. Delayed-type hypersensitivity was observed in 48% of cases. Antitumor immune response was observed in 95% of patients. There were no complete or partial responses; however, a minor response was achieved in one patient with renal cell carcinoma. The stabilization of neoplastic disease was observed in eight patients (seven with malignant melanoma and one with renal cell carcinoma). Median time to tumor progression was 3 months. Conclusions: The approach suggested here appears to be well tolerated and produces a number of durable clinical effects. Further studies are required to determine whether promising effects on immune activation will result in an actual clinical benefit for patients with malignant melanoma and renal cell carcinoma.Keywords
This publication has 31 references indexed in Scilit:
- Vaccination With Irradiated, Autologous Melanoma Cells Engineered to Secrete Granulocyte-Macrophage Colony-Stimulating Factor by Adenoviral-Mediated Gene Transfer Augments Antitumor Immunity in Patients With Metastatic MelanomaJournal of Clinical Oncology, 2003
- Immunization With Melan-A Peptide-Pulsed Peripheral Blood Mononuclear Cells Plus Recombinant Human Interleukin-12 Induces Clinical Activity and T-Cell Responses in Advanced MelanomaJournal of Clinical Oncology, 2003
- Melanoma inhibitor of apoptosis protein (ML-IAP) is a target for immune-mediated tumor destructionProceedings of the National Academy of Sciences, 2003
- T cell defined tumor antigensCurrent Opinion in Immunology, 1997
- In Vivo Cross-Priming of MHC Class I–Restricted Antigens Requires the TAP TransporterImmunity, 1996
- Role of Bone Marrow-Derived Cells in Presenting MHC Class I-Restricted Tumor AntigensScience, 1994
- Tumor Antigens Recognized by T LymphocytesAnnual Review of Immunology, 1994
- Immunization with Interleukin-2 Transfected Melanoma Cells. A Phase I–II Study in Patients with Metastatic Melanoma. University Hospital LeidenHuman Gene Therapy, 1993
- Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity.Proceedings of the National Academy of Sciences, 1993
- Interleukin 2 gene transfer into tumor cells abrogates tumorigenicity and induces protective immunity.The Journal of Experimental Medicine, 1990