Efficient selection of human tumor growth-inhibiting monoclonal antibodies

Herlyn, Dorothee; Herlyn, Meenhard; Ross, Alonzo H.; Ernst, Carolyn S.; Atkinson, Barbara; Koprowski, Hilary

doi:10.1016/0022-1759(84)90041-3

Cited by 105 publications

(57 citation statements)

References 12 publications

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“…The approach is further confounded by the diversity of neoplastic transformations and genetic heterogeneity in the human population. [13][14][15] In contrast to single or multi-parameter antibody-based techniques, cellular morphology analysis is an effective means of cancer screening. For instance, dysplastic and neoplastic cells have been detected in lung sputum on the basis of morphology.…”

Section: Detection and Discrimination Of Tumor Cellsmentioning

confidence: 99%

Cellular Image Analysis and Imaging by Flow Cytometry

Basiji

Ortyn

Liang

et al. 2007

Clinics in Laboratory Medicine

374

288

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SynopsisImaging flow cytometry combines the statistical power and fluorescence sensitivity of standard flow cytometry with the spatial resolution and quantitative morphology of digital microscopy. The technique is a good fit for clinical applications by providing a convenient means for imaging and analyzing cells directly in bodily fluids. Examples are provided of the discrimination of cancerous from normal mammary epithelial cells and the high throughput quantitation of FISH probes in human peripheral blood mononuclear cells. The FISH application will be further enhanced by the integration of extended depth of field imaging technology with the current optical system. Keywordsimaging; flow; cytometry; fluorescence; brightfield; darkfield; multispectral Quantifying Cellular Structure in Health and DiseaseThe eukaryotic cell is a highly structured, three-dimensional object containing a wide range of molecular species. The size, shape, and structure of the cell, as well as the abundance, location, and co-location of any of these constituent biomolecules may be of significance in any given clinical situation or research application. For instance, in hematopoiesis, as cells differentiate and mature, different subsets of molecules are expressed that reflect a specialized functional capacity for that unique cell type (e.g., granulocytes vs. lymphocytes). In general the characterization of this array of constituent molecules by imaging or flow cytometry provides insight into the physiological function of any particular cell or alternatively, pathological changes that may have occurred or accrued. In clinical practice and in research settings, cellular evaluation by imaging technologies and flow cytometry provides significant information reflecting the particular cellular phenotype, both normal and pathological. Microscopy provides a wealth of information, but data acquisition rates are slow and analysis is generally subjective. In flow cytometry, data acquisition is rapid and better suited for the evaluation of pathologies present in low frequency, but the data are only intensity-based, thus lacking the morphology that truly lends credence to the analysis.In addition, the assessment and evaluation of cell samples by imaging and flow cytometric techniques is complicated by a number of factors. For instance, changes in a cell type or aCorresponding author for proofs and reprints:

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Section: Detection and Discrimination Of Tumor Cellsmentioning

confidence: 99%

Cellular Image Analysis and Imaging by Flow Cytometry

Basiji

Ortyn

Liang

et al. 2007

Clinics in Laboratory Medicine

374

288

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“…Both C017-1A and GA733 mAbs have been shown to inhibit the growth of tumor xenografts in nude mice (4,5), pointing out the potential suitability of these mAbs for the therapy of human tumors. When human subjects with gastrointestinal adenocarcinoma were inoculated with mAb C017-1A (Abl), many of the patients produced anti-idiotype antibody (Ab2) that reacted with the binding site of the Abl (6,7).…”

mentioning

confidence: 99%

Sequence investigation of the major gastrointestinal tumor-associated antigen gene family, GA733.

Linnenbach

Wojcierowski

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

109

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The monoclonal antibody-defined, tumorassociated antigen GA733 was purified from the SW948 human colorectal carcinoma cell line and its partial amino acid sequence was determined. By using a synthetic oligonucleotide probe, two recombinants were isolated from a total human genomic library. We prove the existence of a family of GA733 genes. One of the genomic isolates is demonstrated to be an intronless gene, which is transcribed in pancreatic carcinoma cell lines and in placenta. The GA733 proteins were observed to contain sequences homologous to a repeat unit occurring 10 times in thyroglobulin and once in the HLA-DR-associated invariant chain. A more evolutionarily distant relationship was found with the a chain of the interleukin 2 growth factor receptor.Monoclonal antibodies (mAbs) C017-1A and the related GA733 (1) have been extensively evaluated for the diagnosis and therapy of human gastrointestinal tumors. These mAbs were derived from the immunization of mice with a human colorectal adenocarcinoma cell line and a stomach adenocarcinoma cell line, respectively.

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“…23 GA733-␥ recognizes the EGP40 antigen broadly expressed on colon cancers 24 via the chimeric receptor's extracellular immunoglobulin region. This recognition initiates T cell activation and target lysis via intracellular signaling motifs, thereby redirecting T cells to specifically attack colon cancer cells.…”

Section: Discussionmentioning

confidence: 99%