EX-VIVO ACTIVATED MEMORY T-LYMPHOCYTES AS ADOPTIVE CELLULAR THERAPY OF HUMAN RENAL-CELL TUMOR TARGETS WITH POTENTIATION BY CIS-DIAMMINEDICHLOROPLATINUM(II)

Objective To determine if cis-diamminedichloroplatinum(II) (CDDP) enha nces, by immunomodulation, ex vivo anti-tumour cytotoxicity of autolym phocyte therapy (ALT) against; a chemotherapy-resistant tumour, and if lysis is mediated through T-cells, NK-cells, or both. Materials and m ethods Human renal cell carcinoma (RCC) target cells were derived from surgical specimens and incubated in complete medium (CM) with CDDP, o r in CM alone (control group). ALT-cells were prepared from autologous whole peripheral blood mononuclear cells (PBMC) or NK-cell (CD56)-dep leted PBMC obtained before surgery. Tumour cells from each group were labelled with chromium-51 (Cr-51) and used as targets for ALT-cells an d PBMC in a standard (4 h) and delayed (18 h) Cr-51-release assay at v arying effector/target ratios (E:T), Results Tumour cells incubated in CDDP showed enhanced lysis, as measured by the Cr-51-release assay, a t 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 popula tion precluded both the 4 and 18 h tumour cell lysis. Depletion of NK- cells (CD56(+)) diminished the ex vivo lysis of autologous targets dur ing the 4 but not the 18 h assay. ALT-cells derived from two patients demonstrated ex vivo tumour-specificity against autologous and allogen eic RCC. Conclusions These data suggest that: (i) ex vivo activated me mory T-cells are the principal component demonstrating significant tum our-specific cytotoxicity of ALT-cells against RCC tumour targets; (ii ) CDDP may alter the physical properties of tumour cells rendering the m susceptible to immune-mediated attack (iii) the combination of ALT a nd CDDP may lead to increased therapeutic efficacy in patients with me tastatic RCC.