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Biomedical subjects

H Koprowski

Publications and source records attributed to H Koprowski.

At least 361 records · Page 20Linked to original sources

Specific immunoreactivity of hybridoma-secreted monoclonal anti-melanoma antibodies to cultured cells and freshly derived human cells.

The specificities of monoclonal antibodies against melanoma cells were analyzed using radioimmunoassay, mixed-hemadsorption assay, and quantitative absorption on a variety of malignant and nonmalignant cells. Three of the six hybridoma-secreted antibodies bound to the majority of melanoma cell lines, melanoma tumors, and astrocytoma cell lines as well as to all normal and Epstein-Barr virus-transformed lymphocytes tested. The binding pattern coincides with the presence or absence of the DR antigen on human cells. Conversely, two other antibodies, 19-19 and Nu4B, detected two different antigens common to melanoma and astrocytoma cells only. Cloning of melanoma cells resulted in establishment of DR-positive and DR-negative clones, with the binding of Nu4B antibody retained in all.

Animals↗

Inhibition of growth of colorectal carcinoma in nude mice by monoclonal antibody.

Hybridoma-derived monoclonal anti-colorectal carcinoma antibodies suppressed the growth of colorectal carcinoma in nude mice as evidenced by a lower incidence of tumors, a longer latency period, and a smaller volume of tumors in antibody-treated than in control animals. The growth-inhibiting properties of monoclonal anti-colorectal antibodies seem to be specific for colorectal carcinoma cells. This is indicated by the lack of effect of the antibodies on the growth of melanomas or bronchogenic carcinomas and by the binding of the antibodies in vivo to colorectal carcinoma cells but not to lung or kidney cells from tumor-bearing animals or to other tumor cells implanted in other animals. Inhibition of tumor growth was most probably mediated by antibody-dependent cell-mediated cytotoxicity. The results of these studies could provide an approach to the study of immunotherapeutic possibilities for anti-colorectal carcinoma antibodies in humans.

Animals↗

Acute demyelinating disease in a chimpanzee three years after inoculation of brain cells from a patient with MS.

Brain cells from a patient with classic multiple sclerosis were inoculated intracerebrally into the frontal lobe of a newborn chimpanzee. The animal developed acute quadriplegia three years, two months later and was killed four days after the onset of symptoms. Central nervous system lesions were primarily localized in the spinal cord at root entry zones; these were characterized by demyelination and regeneration of myelin by Schwann cells.

Animals↗

Reactivity of monoclonal anti-melanoma antibodies with melanoma cells freshly isolated from primary and metastatic melanoma.

Human melanoma cells, freshly obtained from nine primary and metastatic melanoma cases, were tested for binding of monoclonal anti-melanoma antibodies produced in vitro by hybridoma clones. Monoclonal anti-melanoma antibodies bind to melanoma cells but do not react with nonmalignant cells obtained from the same patients or with cells obtained from giant hairy nevus. These results confirm the existence of tumor-specific antigens. Binding of monoclonal antibodies to melanoma cells of several origins, primary or metastatic, from different patients suggests the existence of tumor antigens shared by human melanoma cells. The binding pattern of different antibodies to various cells also predicts the existence of more than one tumor-specific antigenic determinant on melanoma cells.

Animals↗

Monoclonal antibodies in cell-mediated cytotoxicity against human melanoma and colorectal carcinoma.

Hybridoma-derived monoclonal anti-melanoma antibodies and anti-colorectal carcinoma antibodies were found to mediate in vitro antibody dependent cell-mediated cytotoxicity (ADCC) reactions against melanoma and colorectal carcinoma cells, respectively. The antigen(s) detected in ADCC on melanoma cells maintained for more than one hundred passages in tissue culture were also found on two recently established melanoma cell lines. These antigens were not detected on skin fibroblasts of the same patients from whom the melanomas were obtained. The ADCC reactivities of anti-melanoma and anti-colorectal carcinoma antibodies were found to be specific for melanoma cells and colorectal carcinoma cells, respectively.

Animals↗

Expression of malignancy in hybrids between normal and malignant cells.

Somatic cell hybrids between either normal human fibroblasts, phenotypically normal mouse fibroblasts or mouse peritoneal macrophages and HT1080 human diploid fibrosarcoma cells were studied for their ability to form tumors in nude mice. The results of this study indicate that tumorigenic behavior is expressed as a dominant trait in both human-human and mouse-human hybrid cells.

Animals↗

Colorectal carcinoma antigens detected by hybridoma antibodies.

Hybridoma cells which secrete colorectal carcinoma-specific antibodies have been produced and used to study the antigenic structure of these tumor cells. Nineteen antibodies have been studied in detail, and 15 of these are colorectal carcinoma specific. Only two antibodies reactive with carcinoembryonic antigen (CEA) have been discovered and five other antibodies that react with distinct epitopes on the cell surface have been defined. Several antigens with distinct molecular characteristics have been shown to exist by use of hybridoma antibodies. Six hybridoma antibodies have been shown to mediate antibody-dependent cell-mediated cytotoxicity (ADCC).

Animals↗

Colorectal carcinoma-specific antigen: detection by means of monoclonal antibodies.

Fusion of P3 X 63 Ag8 mouse myeloma cells with splenocytes obtained from mice immunized with cells derived from human colorectal carcinomas resulted in the production of antibody-secreting hybridomas. Two hybridomas (1083-17 and 1116-56) and their clones secreted antibodies binding specifically to human colorectal carcinoma cells either grown in culture or obtained from patients, but did not bind to normal colonic mucosa or other normal and malignant human cells. The binding specificity was consistent in three assays: radioimmunoassay, mixed hemadsorption, and immunofluorescence. Adsorption of these antibodies to colorectal carcinoma cell lines totally eliminated their specific binding.

Antibodies, Neoplasm↗

Detection by complementation of defective or uninducible (herpes simplex type 1) virus genomes latent in human ganglia.

Reconstruction experiments have shown that temperature-sensitive (ts) mutants of herpes simplex virus type 1 (HSV-1)(Glasgow strain 17) grow, complement, and recombine with similar efficiency in human nerve ganglion cells, human brain cells, normal human fibroblasts (WI38), and baby hamster kidney (BHK) 21/C13 hamster cells. Cultures of human trigeminal, superior cervical, and vagus ganglia that had failed to release herpes simplex virus spontaneously were superinfected with a range of ts mutants of HSV-1 and incubated at both permissive (31 degrees C) and nonpermissive (38.5 degrees C) temperatures. Progeny virus was assayed at both temperatures to determine if complementation of or recombination with the input genomes had occurred. The results showed that the ganglia from 8 of 14 individuals, which had been consistently negative for spontaneous release of virus, contained information that could be detected or rescued following superinfection with ts mutants of herpes simplex virus. In two additional cases, positive results were obtained after the superinfection of negative ganglia explants, but in each of these herpes simplex virus had previously been spontaneously released from one of six ganglia explanted.

DNA, Viral↗

Chromosomal location of the genes for human immunoglobulin heavy chains.

We have studied somatic cell hybrids between P3x63Ag8 mouse myeloma cells deficient in hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) and either human peripheral lymphocytes or human lymphoblastoid or myeloma cells for the production of human immunoglobulin chains and for the expression of enzyme markers assigned to each of the different human chromosomes. Human chromosome 14 was the only human chromosome present in all independent hybrids producing mu, gamma, and alpha human heavy chains. In two of the independent hybrids that produced human heavy chains, human chromosome 14 was the only human chromosome present in the hybrid cells. Loss of human chromosome 14 from these hybrids resulted in the concomitant loss of their ability to produce human immunoglobulin heavy chains. In view of these results, we conclude that the genes for human immunoglobulin heavy chains are located on human chromosome 14 in immunoglobulin-producing human cells.

Animals↗

The polypeptide and the DNA restriction enzyme profiles of spontaneous isolates of herpes simplex virus type 1 from explants of human trigeminal, superior cervical and vagus ganglia.

Analysis of the infected cell polypeptides and the DNA restriction profiles of 31 HSV-1 isolates from the trigeminal, superior cervical and vagus ganglia from 17 individuals (12 U.S.A., 2 Japanese, 3 Norwegian) could be classified as 15 different virus strains. With the exception of the three Norwegian isolates which gave identical profiles, virus isolates from the ganglia of different individuals could all be distinguished from one another. In contrast virus isolates from the trigeminal, superior cervical and vagus ganglia of the same individual, or virus isolates from the left and right ganglia of the same individual or multiple isolates from different explants of a single ganglion were indistinguishable. In conclusion, a single virus strain infects each individual initially and virus descended from this event subsequently infects and becomes latent in different cells of the same ganglion as well as in different ganglia.

DNA Restriction Enzymes↗

Cytomegalovirus isolation from a chimpanzee with acute demyelinating disease after inoculation of multiple sclerosis brain cells.

A strain of cytomegalovirus (CMV) was isolated during the third subcultivation of explants from the left frontal lobe of a chimpanzee that developed paralysis more than 3 years after intracerebral inoculation at birth with brain cell cultures derived from a patient with multiple sclerosis. Another strain of CMV was also isolated from a lymph node culture taken from the same chimp. The isolates, designated MZM-13 and MZM-14, produced a cytopathic effect characteristic for CMV when inoculated into brain, ganglion, or fibroblast cultures of human or simian origin. Infected cells contained characteristic Cowdry A intranuclear as well as intracytoplasmic inclusion bodies, and 100-nm spherical herpes-like virus particles were detected by electron microscopy in the nucleus and cytoplasm of infected cells. Virus was further identified as CMV with convalescent human anti-CMV serum. Complement-fixing antibody to CMV was present at a titer of 1:32 when the acutely ill chimpanzee was sacrificed. No antibody was detected at birth or at 1 or 2 years of age. A newborn chimpanzee inoculated intracerebrally with MZM-13 developed clinically asymptomatic lesions in the central nervous system characterized by acute and chronic inflammation and degeneration of myelin in cranial and spinal nerve roots. Restriction endonuclease analysis of viral deoxyribonucleic acid isolated from these two viruses indicated that MZM-13 and MZM-14 are identical and are closely related to chimpanzee CMV. No similarity in restriction endonuclease fragment patterns was found between MZM virus and the Towne and Clegg strains of human CMV.

Animals↗

Morphological studies of hamster brain cells transformed in vitro by a human papovavirus BK.

The cytomorphology and cytogenesis of BK virus-transformed hamster brain cells (HBBK cells) were studied. HBBK cells with indistinct processes showed a tendency to epithelial arrangement as well as characteristics of malignant tumor cells in vitro, and developed long, delicate processes when cell growth was suppressed. Glial fibrillary acidic protein was demonstrated by immunofluorescence in the cytoplasm of almost all HBBK cells. The tumors arising in hamsters after subcutaneous inoculation of HBBK cells were classified as poorly differentiated gliomas. These findings suggest that selective transformation of glial cells in hamster brain cells by BK virus occurred.

Animals↗