Immunotherapy of renal cell carcinoma by intratumoral administration of an IL-2 cDNA/DMRIE/DOPE lipid complex.
Intratumoral administration of cytokine genes in order to achieve paracrine secretion of immunostimulatory cytokines and to create tumor vaccines in situ can avoid difficulties associated with the production of autologous and allogeneic vaccines, and toxicity related to systemic administration of cytokines. In this review, we summarize our experience with intratumoral administration of IL-2 cDNA/DMRIE/DOPE lipid complex in patients with metastatic renal cell carcinoma. An objective response rate of 14% was achieved in a phase I/II clinical trial and was confirmed in the low-risk subgroup of a phase II study. The achieved objective clinical responses (PR/CR) were long lasting. Application of PCR and immunohistochemistry in post-treatment tumor biopsies detected the IL-2 plasmid in addition to increased IL-2 expression in tumor cells and CD8 infiltration. Clinical trials employing higher doses of the plasmid in renal cell carcinoma patients with limited disease are ongoing.
Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
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Daniels
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Galanis
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D002986:Clinical Trials as Topic; D018076:DNA, Complementary / Q000008:administration & dosage* / Q000235:genetics; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D007376:Interleukin-2 / Q000235:genetics*; D007680:Kidney Neoplasms / Q000473:pathology / Q000628:therapy*; D008081:Liposomes; D008545:Melanoma / Q000628:therapy
D018076:DNA, Complementary; D007376:Interleukin-2; D008081:Liposomes