title: Interleukin 2 gene therapy of colorectal carcinoma with autologous irradiated tumor cells and genetically engineered fibroblasts: a Phase I study.
abstract: The purpose of this study was to determine the safety, toxicity, and antitumor immune response following S.C. immunizations with a mixture of irradiated, autologous tumor cells and autologous fibroblasts that were genetically modified to express the gene for interleukin 2 (IL-2) in patients with colorectal carcinoma. Ten patients were treated with a fixed dose of tumor cells (10(7)) and escalating doses of fibroblasts secreting IL-2 (per 24 h): 100 units (three patients), 200 units (three patients), 400 units (three patients), and 800 units (one patient). Pre- and posttreatment peripheral blood mononuclear cells were evaluated for evidence of antitumor immune responses. Fatigue and/or flu-like symptoms were experienced by seven patients and delayed-type hypersensitivity-like skin reactions were observed at the sites of the second or subsequent vaccinations in five patients. Low frequencies of tumor cytotoxic T-cell precursors (range, 1/190,000-1/1,320,000 peripheral blood mononuclear cells) were detected prior to therapy in four of seven patients. There was a 5-fold increase following treatment in the frequency of tumor cytotoxic T-cell precursors in two of six evaluable patients. Some patients with colorectal cancer have low frequencies of tumor cytotoxic T-cell precursors that may be increased by this well-tolerated form of IL-2 gene therapy, which warrants continued clinical evaluation.
authors.affiliation: Sidney Kimmel Cancer Center, Clemma A. Hewitt Gene Therapy Laboratory, San Diego, California 92121-1181, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Sobol
authors.forename: D L
authors.initials: DL
authors.lastname: Shawler
authors.forename: C
authors.initials: C
authors.lastname: Carson
authors.forename: C
authors.initials: C
authors.lastname: Van Beveren
authors.forename: D
authors.initials: D
authors.lastname: Mercola
authors.forename: H
authors.initials: H
authors.lastname: Fakhrai
authors.forename: M A
authors.initials: MA
authors.lastname: Garrett
authors.forename: R
authors.initials: R
authors.lastname: Barone
authors.forename: P
authors.initials: P
authors.lastname: Goldfarb
authors.forename: R M
authors.initials: RM
authors.lastname: Bartholomew
authors.forename: S
authors.initials: S
authors.lastname: Brostoff
authors.forename: D J
authors.initials: DJ
authors.lastname: Carlo
authors.forename: I
authors.initials: I
authors.lastname: Royston
authors.forename: D P
authors.initials: DP
authors.lastname: Gold
mesh_terms: D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D017690:Cell Transplantation; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D005347:Fibroblasts / Q000378:metabolism* / Q000502:physiology / Q000637:transplantation; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000528:radiation effects; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000528:radiation effects / Q000637:transplantation
chemical_list: D019496:Cancer Vaccines; D007376:Interleukin-2