Expression of cDNA libraries from human melanoma, renal cancer, astrocytoma, and Hodgkin disease in Escherichia coli and screening for clones reactive with hightiter IgG antibodies in autologous patient serum lead to the discovery of at least four antigens with a restricted expression pattern in each tumor. Besides antigens known to elicit T-cell responses, such as MAGE-1 and tyrosinase, numerous additional antigens that were overexpressed or specifically expressed in tumors of the same type were identified. Sequence analyses suggest that many of these molecules, besides being the target of a specific immune response, might be of relevance for tumor growth. Antibodies to a given antigen were usually confined to patients with the same tumor type. The unexpected frequency of human tumor antigens, which can be readily defined at the molecular level by the serological analysis of autologous tumor cDNA expression cloning, indicates that human neoplasms elicit multiple specific immune responses in the autologous host and provides diagnostic and therapeutic approaches to human cancer.

Using autologous serum for the immunoscreening of a cDNA expression library derived from tissue involved by Hodgkin's disease, a new 36-kDa protein with the characteristics of galectins (S-type lectins) was detected. Sequence analysis of the cDNA clone HOM-HD-21 revealed two homologous motifs known as lectin domains with galactoside binding capacity. The two domains are linked by a stretch of about 30 amino acid residues and share a sequence homology of 39%. While the N-terminal lectin domain shows merely moderate homologies with known galectins, the C-terminal lectin domain is highly homologous to rat galectin-5 with an amino acid sequence identity of 70%. We ruled out mutations of the tumor-derived transcript by sequence comparison with the respective cDNA cloned from normal peripheral blood leukocytes. Recombinant protein expressed in Chinese hamster ovary cells was purified from lysates by lactose and galactose affinity chromatography, proving the galactoside binding capacity of this new galectin. Northern blot analysis revealed an expression spectrum restricted to peripheral blood leukocytes and lymphatic tissues. In accordance with the nomenclature of known galectins, we suggest to designate this novel galactoside binding protein galectin-9.Galectins, formerly known as S-type lectins or S-Lac lectins (1, 2), are a growing family of soluble animal ␤-galactosidebinding proteins. Members of the galectin family are defined by two characteristic features: affinity to ␤-galactosides and a specific sequence motif called lectin domain. Based on the number of lectin domains two groups of galectins are distinguished. The majority of galectins, including galectin-1, -2, -3, -5, and -7 (3-9), have a single lectin domain. The second group of galectins, which includes rat galectin-4 (10), rat galectin-8 (11), and the 32-kDa galactoside-binding protein of Caenorhabditis elegans (12) is characterized by two tandemly arranged lectin domains connected by a linker peptide. Although none of the galectins contains a typical secretion signal, several galectins are externalized by nonclassical secretory mechanisms (13,14) and play a role in modulating cell-to-cell or cell-to-matrix interactions. Galectins are involved in a number of different cellular events, including physiological (15, 16) and malignant cell adhesion (17, 18), activation and proliferation of immune cells (19,20), as well as induction (21) and inhibition (22) of programmed cell death.Recently, we established SEREX 1 (serological identification of antigens by recombinant expression cloning), a novel approach for the molecular definition of human tumor antigens using autologous serum from tumor patients. For SEREX, tumor-derived -phage expression libraries are screened for reactivity with high-titered IgG antibodies present in the autologous serum of the analyzed patient. By applying this method to several human neoplasms we identified numerous new tumor antigens (23,24). In a cDNA library derived from the Hodgkin's disease-involved spleen of a 28-year-old female...

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Patients with deletions in 22q13 are known to have phenotypic features that include normal or accelerated growth, large hands and feet, hypotonia, delayed psychomotor development and mild facial dysmorphism. To date, very few cases have been investigated by detailed molecular genetic analysis. We have analyzed three new patients with terminal deletions in 22q. We compared the cytogenetic observations with molecular data assessed by fluorescence in situ hybridization and an array of characterized bacterial artificial chromosome recombinants. The shortest region of deletion overlap is localized in 22q13.2-qter distal to the marker D22S94, but the telomeric repeat in the deleted chromosome appears to remain intact. When parental alleles were investigated in two of the three patients, the aberrant homolog was found to be of paternal origin in both cases. Although the deleted region still spans >20 cM, molecular analysis of additional patients and screening for new genes might help in elucidating candidate genes connected with the dysmorphisms defined by deletions of 22q13.