Public health implications of components of plastics manufacture. Emerging concepts of regulation.

Adoptive tumour immunotherapy using human CD4+ T-cells Sir-We read with interest the article by Nakamura et al. describing the generation of large numbers of CD4+CD45RO+ helper/killer T-cells for potential use in adoptive tumour immunotherapy. It is these cells that form the basis for autolymphocyte therapy (ALT). As previously reported, ALT is adoptive tumour immuno-therapy based upon the infusion of CD4+CD45RO+ (memory) T-cells that are activated ex vivo by low doses of the mito-genic monoclonal antibody OKT3, in combination with a previously prepared mixture of autologous cytokines (Celis et al., 1991). We have demonstrated that ex vivo activation of murine splenocytes results in the generation of tumour-specific T-cells with a memory phenotype (Osband et al., 1989). In addition, ex vivo depletion of CD45RO+ T-cells from the autolymphocyte preparation markedly impairs ex vivo lysis of autologous tumour targets (Gold et al., 1993). Monthly infusions of autolymphocytes and daily oral cime-tidine has been shown to be active in patients with metastatic renal cell cancer (Osband et al., 1990; Lavin et al., 1992). Similar to ALT, the cells generated by the methodology of Nakamura et al. were made up mostly of the CD45RO+ subset of CD4+ T-cells. There are however, two important distinctions and issues that need to be addressed regarding both autolymphocytes and the CD4+ helper/killer T-cells of the report by Nakamura et al. The first is that autolymphocytes are derived ex vivo from activation of unseparated peripheral blood lymphocytes (PBL). As stated, it has been shown that non-specific ex vivo activation of murine splenocytes results in the generation of autolymphocytes that are tumour-specific (Osband et al., 1989) and that high levels of interleukin (IL)-1 rather than IL-2 in human ex vivo cell cultures correlate with improved clinical efficacy (Osband et al., 1990; Lavin et al., 1992). Therefore, it may not be necessary to separate the CD4+ T-cell subset from PBL, and in fact may be clinically advantageous and physiologic to activate and then infuse memory T-cells as part of a heterogeneous cell population for adoptive tumour immunotherapy (Panzer et al., 1990). The second distinction involves the actual number of cells to be infused. A commonly held belief in adoptive tumour immunotherapy is that 'more is better'. That is, the greater number of cells that one wishes to infuse, the better for the patient. However, this may not be the case as it has been demonstrated with ALT that more cells are not …