Ex vivo activated memory T‐Iymphocytes as adoptive cellular therapy of human renal cell tumour targets with potentiation by cis‐diamminedichloroplatinum(II)

Objective To determine if cis‐diamminedichloroplat‐inum(II) (CDDP) enhances, by immune‐modulation, 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. Materials and 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 (4h) 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.