Indolent CD8-positive lymphoid proliferation of acral sites is a distinctive and readily identifiable entity and should be included in the next consensus revision of cutaneous lymphoma classification. Although cases described thus far have followed an indolent clinical course, dermatologists should remain guarded about the prognosis and full staging and longitudinal observation are recommended until this condition is better understood.

Chimeric T cell receptors with specificity for tumor-associapletely humanized chimeric receptor. After transfection, the ted antigens are successfully used to target T cells to humBW431/26 scFv-CH2CH3-␥ receptor is expressed as tumor cells. The efficacy of this approach, however, is a homodimer on the surface of MD45 T cells. Co-incureduced by soluble antigen that is frequently present in bation with CEA + tumor cells specifically activates grafted high serum concentrations. To overcome this situation, we MD45 T cells indicated by IL-2 secretion and cytolytic constructed an anti-CEA chimeric receptor whose extraactivity against CEA + tumor cells. Notably, the efficacy of cellular moiety is composed of a humanized single chain receptor-mediated activation is not affected by soluble CEA antibody fragment (scFv) derived from the anti-CEA mAb up to 25 g/ml demonstrating the usefulness of this chim-BW431/26 and the CH2/CH3 constant domains of human eric receptor for specific cellular activation by membraneIgG. The intracellular moiety consists of the ␥-signaling bound CEA even in the presence of high concentrations of chain of the human Fc⑀RI receptor constituting a com-CEA, as found in patients during progression of the disease.Keywords: chimeric T cell receptor; scFv; membrane-bound CEAIn a recently developed strategy for the cellular immunotherapy of malignant diseases, the advantages of antibody-based targeting and cell-mediated cytolysis have been combined by grafting effector cells with a chimeric receptor that binds to a tumor-associated antigen. 1-5 The antigen-binding domain of the receptor is composed of a single-chain antibody fragment (scFv) derived from the heavy (VH) and light (VL) chain variable regions of a monoclonal antibody (mAb). The intracellular signalling domain is derived from the cytoplasmic part of a membrane-bound receptor involved in cellular activation. After grafting cytotoxic T cells with the chimeric receptor, an antigen-specific and MHC-unrestricted cellular immune response is directed to cells expressing the particular mAb-defined antigen (for review, Refs 6 and 7).Due to xenogeneic parts of the chimeric receptor, the efficacy in the therapy of malignant diseases, however, will be negatively influenced by the potential of a hostversus-graft reaction. In addition, soluble antigen frequently present in high concentrations in the serum of cancer patients will block the receptor of grafted effector cells thus preventing tumor cell recognition and antigendriven cellular activation upon specific receptor crosslinking. 6,8 This limitation so far restricts the chimeric receptor approach to those patients with very low amounts of soluble antigen unlikely to prevent effector cell-tumor cell interaction. Malignant tumors, however, that express carcinoembryonic antigen (CEA) are frequently accompanied by high serum concentrations of soluble CEA. 9 In this particular situation the application of the chimeric receptor-based strategy requires a receptor whose tumor cell recognition and effector cel...

Recombinant T‐cell receptors with antibody‐like specificity for tumor‐associated antigens are successfully used to direct the cytolytic activity of T cells toward tumor cells. Clinical application, however, needs to comply with the low immunogenicity of the recombinant receptor, efficient gene transfer into peripheral blood T cells, and enrichment of receptor‐grafted cells. Here, we address these issues and describe an entirely humanized immune receptor for use in adoptive immunotherapy of colorectal carcinoma. The receptor consists of a single‐chain antibody (scFv) binding domain specific for carcinoembryonic antigen (CEA), the IgG hinge and CH2/CH3 (Fc) joining region, and the transmembrane and intracellular CD3 ζ signaling chain. To express the receptor in peripheral blood T cells, both GALV envelope and MuLV 4070A pseudotyped retrovirus turned out to be equally efficient, with transduction efficiencies of about 5% to 40%, depending on the lymphocyte donor. Furthermore, receptor‐grafted T cells could be 2‐ to 6‐fold enriched by magnetic activated cell sorting, utilizing an antibody directed to the extracellular IgG domain of the receptor. Upon co‐culture with CEA+ tumor cells, receptor‐grafted T cells are specifically and efficiently activated to cytolysis and IFN‐γ secretion, demonstrating their feasibility for the adoptive immunotherapy of CEA+ carcinomas. Int. J. Cancer 88:115–120, 2000. © 2000 Wiley‐Liss, Inc.

We describe three generations of a white family with autosomal dominant chronic mucocutaneous candidiasis (CMCC) and primary hypothyroidism, which was complicated by squamous cell carcinoma (SCC) of the oesophagus in the index case. We report this family to increase awareness of this rare autosomal dominant variant of CMCC endocrinopathy syndrome associated with primary hypothyroidism without evidence of autoimmune endocrinopathy, and to highlight the risk of developing oesophageal SCC at a young age as a fatal complication of CMCC.

Recombinant T-cell receptors with antibody-like specificity for tumor-associated antigens are successfully used to direct the cytolytic activity of T cells toward tumor cells. Clinical application, however, needs to comply with the low immunogenicity of the recombinant receptor, efficient gene transfer into peripheral blood T cells, and enrichment of receptor-grafted cells. Here, we address these issues and describe an entirely humanized immune receptor for use in adoptive immunotherapy of colorectal carcinoma. The receptor consists of a single-chain antibody (scFv) binding domain specific for carcinoembryonic antigen (CEA), the IgG hinge and CH2/CH3 (Fc) joining region, and the transmembrane and intracellular CD3 zeta signaling chain. To express the receptor in peripheral blood T cells, both GALV envelope and MuLV 4070A pseudotyped retrovirus turned out to be equally efficient, with transduction efficiencies of about 5% to 40%, depending on the lymphocyte donor. Furthermore, receptor-grafted T cells could be 2- to 6-fold enriched by magnetic activated cell sorting, utilizing an antibody directed to the extracellular IgG domain of the receptor. Upon co-culture with CEA(+) tumor cells, receptor-grafted T cells are specifically and efficiently activated to cytolysis and IFN-gamma secretion, demonstrating their feasibility for the adoptive immunotherapy of CEA(+) carcinomas.