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I Hellström

Publications and source records attributed to I Hellström.

At least 145 records · Page 8Linked to original sources
PubMed1982

Characterization of a human melanoma-associated ganglioside antigen defined by a monoclonal antibody, 4.2.

A monoclonal IgM antibody, 4.2, reacting with a surface antigen expressed on most human melanomas (Yeh, M.-I., Hellström, I., Abe, K., Hakomori, S., and Hellström, K. E. (1982) Int. J. Cancer, 29, 269-275) was shown to be directed to a ganglioside with the carbohydrate structure NeuAc alpha 2 leads to 8NeuAc alpha 2 leads to 3Gal beta 1 leads to 4Glc beta 1 leads to 1Cer. The carbohydrate structure, established by enzymatic degradation and methylation analysis with mass spectrometry, is identical with that of brain GD3 ganglioside, but its ceramide is characterized by a predominance of longer chain fatty acids, in contrast to brain GD3 that has mainly C18:0 fatty acid. The antibody did not react with various other gangliosides, including those having the same terminal sugar sequence (NeuAc alpha 2 leads to 8NeuAc alpha 2 leads to 3Gal) as GD3, such as GT1a and GQ1b. Its specificity is therefore restricted to the NeuAc alpha 2 leads to 8NeuAc alpha 2 leads to 3Gal beta 1 leads to 4Glc leads to Cer sequence, including the innermost sugar, Glc residue.

Antibodies, Monoclonal↗
PubMed1982

Human melanoma cells can be killed in vitro by an immunotoxin specific for melanoma-associated antigen p97.

Conjugates (immunotoxins) comprising ricin A-chain and monoclonal antibody 96.5, which is specific for human melanoma-associated antigen p97, inhibited protein synthesis and colony formation of cultured human melanoma cells that expressed more than 80,000 molecules of p97 per cell. Cells expressing fewer than 5,000 molecules of p97 were not killed. The presence of 10 mM ammonium chloride significantly increased the efficiency of the immunotoxin, tumor cells expressing high levels of p97 being killed at immunotoxin concentrations as low as 10(-10) M.

Antibodies, Neoplasm↗
PubMed1982

A cell-surface antigen which is present in the ganglioside fraction and shared by human melanomas.

We have raised a hybridoma, 4.2, which forms an IgM antibody to an antigen expressed on cultivated cells from most human melanomas, more infrequently on cells from other human tumors, and very weakly on cultivated fibroblasts, T cells and B cells. The antigen can be detected in biopsy material of human melanoma and, in smaller amounts, in fresh samples of normal human lung and kidney. Preliminary biochemical characterization indicates that it is associated with the ganglioside fraction. We feel that the antigen (referred to as 4.2) has a sufficient degree of tumor specificity to be rated as a human melanoma-associated antigen.

Antibodies, Monoclonal↗
PubMed1982

Monoclonal antibodies to two mouse bladder carcinoma antigens.

Carcinomas of the urinary bladder of mice were induced by 3-methyl-cholanthrene or fanft [(4-5-nitro-2-furyl)-2-thioazolyl formamide]. On transplantation in vivo, tumor lines consisting of well-differentiated transitional-cell carcinomas were established. Some tumors were also explanted in vitro. A rat was immunized with a pool of carcinomas and normal bladder tissue and its spleen cells were hybridized with NS-l mouse myeloma cells. Supernatants of hybrid cells ("hybridomas") were screened for antibody binding to antigens present in bladder carcinomas but not in normal syngeneic urinary bladder, with cell extracts as targets. Hybridomas that appeared to have the required specificity were cloned, tested further against transitional-cell bladder carcinomas, an anaplastic bladder tumor, rhabdomyosarcomas, a mammary carcinoma, myelomas and lymphomas, and normal adult urinary bladder, kidney, lung, spleen, heart, brain, thymus, and whole embryo. Antibody formed by one hybridoma, 2H5, gave significant binding to membranes from five of seven transitional-cell carcinomas but not to membranes from many other tissues. A second hybridoma, IE6, formed antibody to an antigen present in bladder carcinomas and normal liver and, in smaller amounts, in several other normal and neoplastic tissues. Fluorescence microscopy established that both antigens were present at the cell surface of transitional-cell bladder carcinomas. Immunoprecipitation and SDS-polyacrylamide gel electrophoresis were used to identify the target antigens from 125I-labelled cell membrane proteins. The antibody formed by 2H5 was found to identify a protein with a molecular weight in the range of 140 kilodaltons, which was detected in transitional-cell bladder. The molecular nature of the antigen defined by hybridoma IE6 is not known.

Animals↗
PubMed1982

Workshop on monoclonal antibodies to human melanoma-associated antigens: findings of the Seattle group.

The 30 workshop monoclonal antibodies identify a number of distinct cell surface antigens of human melanoma. Indirect 125I-protein A binding assays showed that virtually all of the antibodies recognized antigens at the surface of SK-MEL-28 melanoma cells. Immunoprecipitation from detergent lysates of surface-radioiodinated cells showed that 16 of the antibodies recognized cell surface proteins. Antibodies 96.5, 118.1, 133.2 and two antibodies from the Sloan-Kettering group, I12 and L10, recognized a 97,000 MW protein, p97, but none of the other antibodies did so. Many of the antigens appear to have sufficient specificity for melanoma to be of interest as potential diagnostic markers and therapeutic targets and to merit structural and functional studies.

Antibodies, Monoclonal↗
PubMed1982

Cell surface phenotypes of radiolabeled immune long-lived lymphocytes that selectively localize in syngeneic tumours.

Using a cell separation technique to isolate mononuclear leukocytes from solid tumors in conjunction with combined radioautography and two-color immunofluorescence, we have characterized the surface markers of 3H-labeled, immune, long-lived, small lymphocytes (LLSLs) that selectively localize into chemically induced sarcomas. When small tumor pieces were implanted into immune mice whose LLSLs had been radiolabeled, the LLSLs that selectively localized into those tumors to which the hosts had been immunized were predominantly Thy-1+, Lyt-1+2-. Localization into the appropriate tumor was also detected upon adoptive transfer of immune LLSLs to tumor-bearing mice, especially when these mice had, before transfer, received 400 rads of whole-body irradiation. These 3H-labeled LLSLs were also found to be predominantly Thy-1+, Lyt-1+2-.

Animals↗
PubMed1981

Production of T-cell lines with inhibitory or stimulatory activity against syngeneic tumors in vivo. A preliminary report.

We obtained Thy-I-positive cells directly from growing methylcholanthrene-induced (MCA-1510) sarcomas using fluorescence-activated cell sorting, then cultured these lymphocytes in medium containing Interleukin-2 and tested their activity in vivo against various MCA-sarcoma lines with the Winn assay. We found that cultured T cells from small MCA-1510 tumors (17 days after transplantation) significantly inhibited the growth of that particular sarcoma, but not of three other MCA-tumor lines tested, while cultured T cells from large MCA-1510 sarcomas (41 days after transplantation) significantly enhanced the growth of that tumor, but not of an unrelated tumor, MCA-1460. The former cells were primarily Lyt-1+, 2+ while the latter were primarily Lyt-1+, 2+.

Animals↗
PubMed1981

Species restriction of a monoclonal antibody reacting with residues 130 to 137 in encephalitogenic myelin basic protein.

A monoclonal antibody (immunoglobulin G1) has been produced that reacts against myelin basic protein present in or extracted from the brains of many mammals-with certain important exceptions. Because of known species differences in amino acid sequences of basic protein and of certain peptide fragments, the binding site for this particular antibody appeared likely to include residues 130 to 137. Confirmation of this hypothesis was obtained by amino acid composition of the major immunoreactive peptides produced by thermolysin digestion of human basic protein and isolated by high-performance liquid chromatography.

Amino Acid Sequence↗
PubMed1981

Suppressor pathways in tumor immunity: a requirement for Qa-1 positive tumor-bearer spleen T cells in suppression of the afferent immune response to tumor antigens.

Spleen cells from mice bearing large methylcholanthrene (MCA)-induced sarcomas were injected intravenously into mice challenged in the hind footpads with heavily-irradiated cells from the same or a different sarcoma. As measured by [3H]-thymidine incorporation on day 5 or 6, cellular proliferation in the draining popliteal lymph nodes of these mice was significantly depressed as compared to control animals receiving normal spleen cells or medium intravenously. The suppression was found to be mediated by a Qa-1-positive, Thy-1 positive cell. It was relatively resistant to cyclophosphamide treatment (100 mg/kg). Furthermore, it had both antigen-specific and non-specific components. The findings are discussed in relation to a suppressor activator cell-suppressor acceptor cell pathway in the immunoregulation of tumor immunity.

Animals↗
PubMed1981

Two human tumor-associated antigens, p155 and p210, detected by monoclonal antibodies.

BALB/c mice were immunized with human melanoma cells and their spleen cells hybridized with NS-1 myeloma cells. The hybrids were screened for the production of antibodies that bound to melanoma cells. Two hybridomas of interesting specificity were identified and cloned. Hybridoma 5.1 produce an IgG1 antibody that binds to about half of the melanomas and carcinomas tested. The target is a polypeptide with an apparent molecular weight of 210 kilodaltons on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The antigen, denoted p210, is also expressed in normal adult brain and in certain fetal tissues. Hybridoma 6.1 produces an IgM antibody that binds to about 50% of the melanomas, and 80% of the kidney carcinomas tested. The antigen defined by this antibody in melanomas has an apparent molecular weight of 155 kilodaltons and is denoted p155. It has not been observed on any normal adult or fetal tissues. The antigen present in the kidney carcinomas was not p155, but rather consisted of two proteins of approximately 60,000 and 250,000-300,000 daltons. This observation suggests the possibility that the antigenic determinant recognized by antibody 6.1 may be present on several distinct protein molecules.

Adult↗
PubMed1981

Lymphocyte-dependent antibodies to antigen 3.1, a cell-surface antigen expressed by a subgroup of human melanomas.

Previous work from our laboratory has led to the isolation of a monoclonal IgG2a mouse antibody, 3.2, which is specific for an antigen, 3.1, that is strongest expressed by a group of human melanomas. We have no demonstrated that this antibody can mediate antibody-dependent cellular cytotoxicity (ADCC) to human melanoma cells expressing antigen 3., and that lymphocytes from human peripheral blood can be used as the source of K cells. A monoclonal IgG1 antibody, 3.1, to the same determinant of antigen 3.1 gave only weak and inconsistent ADCC.

Animals↗
PubMed1981

Analysis of normal neoplastic human tissues for the tumor-associated protein p97.

We have used immunoprecipitation to test tumor biopsies and normal adult and fetal human tissues for p97, a tumor-associated protein. Five of nine melanoma biopsies contained p97 in low to very high levels. Three of seven non-melanoma tumors contained p97, but in smaller amounts. No p97 was detected in any of the normal adult tissues examined. The protein was, however, observed in samples of fetal colon and umbilical cord, and in one sample of fetal lung. One of two benign nevi contained high levels of p97, whole on benign angiofibroma was negative. We conclude that the presence of p97, in levels detectable by our method, appears to be characteristic of certain neoplastic and fetal tissues.

Adult↗