title: Ex vivo activated memory T-lymphocytes as adoptive cellular therapy of human renal cell tumour targets with potentiation by cis-diamminedichloroplatinum(II).
abstract: OBJECTIVE
  To determine if cis-diamminedichloroplatinum(II) (CDDP) enhances, by immunomodulation, ex vivo anti-tumour cytotoxicity of autolymphocyte therapy (ALT) against a chemotherapy-resistant tumour, and if lysis is mediated through T-cells, NK-cells, or both.
  
  
  METHODS
  Human renal cell carcinoma (RCC) target cells were derived from surgical specimens and incubated in complete medium (CM) with CDDP, or in CM alone (control group). ALT-cells were prepared from autologous whole peripheral blood mononuclear cells (PBMC) or NK-cell (CD56)-depleted PBMC obtained before surgery. Tumour cells from each group were labelled with chromium-51(51Cr) and used as targets for ALT-cells and PBMC in a standard (4 h) and delayed (18 h) 51Cr-release assay at varying effector/target ratios (E:T).
  
  
  RESULTS
  Tumour cells incubated in CDDP showed enhanced lysis, as measured by the 51Cr-release assay, at all E:T tested. This lysis was significantly greater during the 18 h assay and when ALT-cells were used as the effector cells rather than PBMC. Depletion of CD45RO+ (memory) T-cells from the ALT cell population precluded both the 4 and 18 h tumour cell lysis. Depletion of NK-cells (CD56+) diminished the ex vivo lysis of autologous targets during the 4 but not the 18 h assay. ALT-cells derived from two patients demonstrated ex vivo tumour-specificity against autologous and allogeneic RCC.
  
  
  CONCLUSIONS
  These data suggest that: (i) ex vivo activated memory T-cells are the principal component demonstrating significant tumour-specific cytotoxicity of ALT-cells against RCC tumour targets; (ii) CDDP may alter the physical properties of tumour cells rendering them susceptible to immune-mediated attack; (iii) the combination of ALT and CDDP may lead to increased therapeutic efficacy in patients with metastatic RCC.
authors.affiliation: Division of Haematology, Mount Sinai Hospital, New York, NY, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Gold
authors.forename: T R
authors.initials: TR
authors.lastname: Masters
authors.forename: B
authors.initials: B
authors.lastname: Babbit
authors.forename: E M
authors.initials: EM
authors.lastname: Fine
authors.forename: H N
authors.initials: HN
authors.lastname: Weber
authors.forename: P D
authors.initials: PD
authors.lastname: Unger
authors.forename: I
authors.initials: I
authors.lastname: Leventhal
authors.forename: C D
authors.initials: CD
authors.lastname: Zippe
authors.forename: M E
authors.initials: ME
authors.lastname: Osband
mesh_terms: D002292:Carcinoma, Renal Cell / Q000628:therapy*; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007680:Kidney Neoplasms / Q000628:therapy*; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: C034297:diamminediaqua platinum(II); D002945:Cisplatin