Human melanoma originates in the skin and can lead to widespread metastatic disease. Analysis of melanoma biopsy material has shown that the vitronectin receptor, integrin av#3, is a specific marker of the most malignant cells, i.e., vertically invasive primary lesions or distant metastases (Albelda, S. M.,

A mouse/human chimeric antibody (ch14.18) was developed that reacts with the disialoganglioside GD2 on the surface of tumor cells of neuroectodermal origin. ch14.18 has the constant regions of a human IgG1 antibody and was expressed in a murine hybridoma. This antibody was produced in tissue culture at concentrations up to 180 mg/liter of spent culture fluid. ch14.18 was characterized and compared to 14.G2a, a murine mAb against GD2 of IgG2a isotype derived from the same parental hybridoma as ch14.18. Scatchard plot analysis of data from saturation binding studies on M21 melanoma cells showed identical binding for ch14.18 and 14.G2a. Indirect immunofluorescence revealed the same staining pattern for ch14.18 and 14.G2a on different melanoma cell lines. Both antibodies were equally capable of targeting M21 xenografts in athymic nude mice. ch14.18- and 14.G2a-activated human C-mediated cytolysis of melanoma cell; however, ch14.18-mediated antibody-dependent cytotoxicity of human effector cells against melanoma cells 50- to 100-fold more efficiently than 14.G2a.

Recent advances in cutaneous immunobiology have led to the realization that skin is an important and unique immunologic organ. Studies on the immunobiology of skin cancers induced by ultraviolet radiation indicate that immune mechanisms can play a crucial role in the development of cutaneous tumors. This paper summarizes the evidence linking skin and the immune system and discusses current hypotheses concerning the mechanisms by which UV radiation interferes with cutaneous immunity. The significance of these findings for cutaneous carcinogenesis is discussed.

Clinical resistance of malignant tumors against cytostatic agents is a major obstacle to effective chemotherapy. A cell surface molecule (P-170) which acts as a pump has been identified as the underlying mechanism of the so-called multidrug resistance (MDR). Several compounds have been identified which can effectively block the action of P-170 and are able to render resistant tumor cells chemosensitive. Unfortunately, most modulators display intolerable side effects at therapeutic doses and are therefore not useful clinically. Preclinical studies show that dexverapamil (D-VPM), an optical isomer of the MDR modulator verapamil (Isoptin®), is able to effectively block the function of P-170. Cardiovascular effects are significantly reduced as compared to racemic verapamil, permitting dose escalations to plasma levels which modulate MDR in vitro assays. Promising clinical responses were observed in lymphoma patients, especially in the non-Hodgkin population. These encouraging trials deserve thorough succession studies.