title: T-cell adoptive immunotherapy of metastatic renal cell carcinoma.
abstract: OBJECTIVE
  To determine the feasibility and toxicity of the adoptive transfer of ex vivo-activated T lymphocytes that have been sensitized to autologous tumor vaccine in vivo.
  
  
  METHODS
  Twenty patients with extensive metastatic renal cell carcinoma received systemic adoptive immunotherapy with autologous T cells in the absence of conjunctional interleukin-2 (IL-2) administration. Patients were vaccinated intradermally with irradiated autologous tumor cells and granulocyte-macrophage colony-stimulating factor as an adjuvant to stimulate an immune response. Inguinal lymph nodes draining the vaccine site were surgically removed, and the cells were stimulated with staphylococcal enterotoxin A followed by expansion in 60 IU/mL IL-2, and in some cases additionally stimulated with anti-CD3 monoclonal antibody and IL-2, to obtain a large number of cells.
  
  
  RESULTS
  The staphylococcal enterotoxin A/IL-2 activation induced vigorous proliferation of T cells (median expansion 26-fold) that were a mixture of CD4 and CD8 T lymphocytes. Activated cells were infused intravenously at doses ranging from 2x10(9) to 9.5x10(10). There was minimal toxicity consisting of grade 1 or 2 fever and nausea, and the entire treatment was delivered as outpatient therapy. One patient had a partial response, one had a mixed response, and 8 had stable disease lasting at least 5 months.
  
  
  CONCLUSIONS
  Adoptive transfer of ex vivo-activated, tumor vaccine-primed lymph node cells is feasible and is associated with minimal toxicity when used alone. These results warrant further study in a Phase II trial.
authors.affiliation: Center for Surgery Research, Experimental Therapeutics Program and Department of Urology, Cleveland Clinic Foundation, Ohio, USA.
authors.forename: G E
authors.initials: GE
authors.lastname: Plautz
authors.forename: R M
authors.initials: RM
authors.lastname: Bukowski
authors.forename: A C
authors.initials: AC
authors.lastname: Novick
authors.forename: E A
authors.initials: EA
authors.lastname: Klein
authors.forename: E D
authors.initials: ED
authors.lastname: Kursh
authors.forename: T E
authors.initials: TE
authors.lastname: Olencki
authors.forename: R J
authors.initials: RJ
authors.lastname: Yetman
authors.forename: A
authors.initials: A
authors.lastname: Pienkny
authors.forename: K
authors.initials: K
authors.lastname: Sandstrom
authors.forename: S
authors.initials: S
authors.lastname: Shu
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000556:secondary* / Q000628:therapy*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D007680:Kidney Neoplasms; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes