lewis-y-antigen and Lung-Neoplasms

To identify the mechanism of down-regulation of Lewis Y antigen caused by X-ray irradiation.. The present original research study was conducted at Zhejiang University City College, Hangzhou, Republic of China, from 2020 to 2022. Western blotting, Co-immunoprecipitation (CO-IP), electrophoretic mobility shift assay and Cell Counting Kit-8 (CCK8) were performed to confirm the effect of X-ray irradiation on A549 cell proliferation and its mechanism. Data was analysed using Statistical Package for Social Sciences (SPSS) 11.5.. The expressions of fucosyltransferase IV and Lewis Y were decreased after X-ray irradiation, thus inhibiting the proliferation of A549 lung cancer cells. Deoxyribonucleic acid damage caused by the irradiation caused higher level of poly- adenosinediphosphate-ribosylated Specific Protein 1(SP1), and translocation of SP1 from the nucleus, decreasing the expression of fucosyltransferase IV and Lewis Y.. There was a significant role of glycosylation in radiation therapy for lung cancer.

Topics: A549 Cells; Cell Line, Tumor; Cell Proliferation; Fucosyltransferases; Humans; Lewis Blood Group Antigens; Lung Neoplasms; Sp1 Transcription Factor; X-Rays

We investigated the effect of shed antigen mesothelin on the tumor uptake of amatuximab, a therapeutic anti-mesothelin mAb clinically tested in mesothelioma patients. The B3 mAb targeting a nonshed antigen was also analyzed for comparison. The mouse model implanted with A431/H9 tumor, which expresses both shed mesothelin and nonshed Lewis-Y antigen, provided an ideal system to compare the biodistribution and PET imaging profiles of the two mAbs. Our study demonstrated that the tumor and organ uptakes of

Topics: Animals; Antibodies, Monoclonal; Antigens, Neoplasm; Cell Line, Tumor; Cell-Derived Microparticles; GPI-Linked Proteins; Half-Life; Heterografts; Lewis Blood Group Antigens; Lung Neoplasms; Mesothelin; Mesothelioma; Mesothelioma, Malignant; Mice; Radioisotopes; Tissue Distribution; Zirconium

Tumor-associated macrophages (TAMs) are key components of tumor microenvironment (TME) during tumorigenesis and progression. However, the role of TAMs in lung adenocarcinoma is still unclear. In this study, we aimed to clarify the mechanism underlying the crosstalk between TAMs and epithelial-mesenchymal transition (EMT) of lung adenocarcinoma. Fucosyltransferase IV (FUT4) and its synthetic cancer sugar antigen Lewis Y (LeY) was aberrantly elevated in various solid tumors, it plays critical role in the invasion and metastasis. Here, we found that in lung adenocarcinoma samples, the density of TAMs correlates with E-cadherin level and LeY level. In vitro assays, M2 macrophages promoted FUT4/LeY expression through the transforming growth factor-β1(TGF-β1)/Smad2/3 signaling pathway. FUT4/LeY was indispensable in M2 macrophages-mediated cytoskeletal remodeling and EMT. Furthermore, fucosylation of Ezrin mediated by FUT4/LeY can promote the phosphorylation of Ezrin, which was the critical mechanism of M2 macrophages-induced EMT. In vivo assays confirmed that M2 macrophages promoted EMT through the up-regulation of LeY and phosphorylated Ezrin. Together, our results revealed that TAMs promote Ezrin phosphorylation-mediated EMT in lung adenocarcinoma through FUT4/LeY- mediated fucosylation. Targeting this newly identified signaling may offer new possibilities for immunotherapy in lung adenocarcinoma.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Animals; Biomarkers; Cadherins; Cell Count; Cell Line, Tumor; Cytoskeletal Proteins; Cytoskeleton; Disease Models, Animal; Epithelial-Mesenchymal Transition; Female; Fucosyltransferases; Heterografts; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Lung Neoplasms; Macrophages; Mice; Models, Biological; Phosphorylation; Signal Transduction; Smad2 Protein; Smad3 Protein; Transforming Growth Factor beta1; Up-Regulation

The advantage of tissue microarray (TMA) is its ability to efficiently analyze large numbers of tissue specimens in a methodologically uniform way. The reliability of TMAs, especially with regard to clinicopathological characterizations, when compared to conventional immunohistochemistry (IHC) was evaluated.. Seventy-two embedded tissue sections from lung cancer specimens were stained with monoclonal antibodies against the tumor-associated markers TA-MUC1 and Lewis Y. Three representative cores of every tumor were embedded in a paraffin array multiblock. The IHC was evaluated by the immunoreactive score (IRS).. The data for the TMA IHC and the conventional IHC were concordant (kappa > or = 80%) for both markers. Likewise, discordance (McNemar's test) was low, and sensitivity and specificity were above 80% for both markers. In the samples with high positive expression, the concordance increased (kappa > or = 90%), discordance disappeared (McNemar p = 1.0), and sensitivity and specificity increased above 90% for both markers. Using Cox regression models, all the clinicopathological dependencies were equivalent for both techniques and both markers.. Immunohistochemistry with tissue microarrays is valid and provides results equivalent to conventional immunohistochemistry with respect to expression patterns and clinicopathological characterizations.

Topics: Aged; Antibodies, Monoclonal; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Female; Humans; Immunohistochemistry; Lewis Blood Group Antigens; Lung Neoplasms; Male; Middle Aged; Mucin-1; Prognosis; Staining and Labeling; Tissue Array Analysis

To assess the value of data set coregistration of gamma camera and computed tomography (CT) in the assessment of targeting of humanized monoclonal antibody 3S193 labeled with indium-111 ((111)In-hu3S193) to small cell lung cancer (SCLC).. Ten patients (6 male and 4 female; mean age+/-S.D., 60+/-4 years), from an overall population of 20 patients with SCLCs expressing Lewis Y antigen at immunohistochemical analysis, completed a four weekly injections of (111)In-hu3S193 and underwent gamma camera imaging. All had had, as part of their baseline evaluation, Fluorine18 fluoro-2-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). Two readers in consensus retrospectively coregistered the gamma camera images with the CT component of the FDG PET/CT by automatic or manual alignment. The resulting image sets were visually examined and SCLC lesions targeting at coregistered gamma camera and CT was correlated side-by-side with the (18)F-FDG uptake.. A total number of 31 lesions from SCLC with a thoracic (n=13) or extrathoracic location (n=18) were all positive on FDG PET/CT. Coregistration of the gamma camera to the CT demonstrated targeting of antibody to all lesions >2 cm (n=20) and in a few lesions < or =2 cm (n=2), with no visualization of most lesions < or = 2 cm (n=9). No (111)In-hu3S193 uptake in normal tissues was observed.. Coregistration of antibody gamma camera imaging to FDG PET/CT is feasible and allows valuable assessment of (111)In-hu3S193 antibody targeting to SCLC lesions >2cm, while lesions < or =2 cm reveal a limited targeting.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Female; Gamma Cameras; History, 18th Century; Humans; Indium Radioisotopes; Lewis Blood Group Antigens; Lung Neoplasms; Male; Middle Aged; Pilot Projects; Radioimmunotherapy; Radionuclide Imaging; Small Cell Lung Carcinoma; Tomography, X-Ray Computed; Treatment Outcome; Whole Body Imaging

Lewis Y (Le(y)) is a blood group antigen with robust expression on the surface of epithelial tumors, including small cell lung cancer (SCLC), making it a potential target for antibody-based immunotherapy. 3S193, an immunoglobulin G3 monoclonal antibody, has demonstrated superior specificity, affinity, and cytotoxicity over other anti-Le(y) antibodies. A phase I trial of humanized 3S193 (hu3S193) with dosing up to 40 mg/m2 demonstrated tumor targeting without serious toxicities or the development of human anti-human antibodies.. We tested the targeting and pharmacokinetics of hu3S193 in patients with SCLC. Eligibility required progressive SCLC treated with up to three previous chemotherapy regimens, measurable disease not previously irradiated, and tumor samples positive for 3S193 by immunohistochemistry. Patients received four weekly injections of hu3S193, five patients at 10 mg/m2 and five patients at 20 mg/m2. The first and fourth injections were radiolabeled with indium-111 for gamma camera imaging.. Of 40 patients screened, 25 of 34 (74%) assessable SCLC tumor samples were 3S193 positive by immunohistochemistry. Ten patients were treated with hu3S193; nine completed all four injections. All fluorodeoxyglucose (FDG)-avid lesions >2 cm were visualized on antibody single-photon emission computed tomography. Some lesions overlying vascular structures could not be visualized. No difference was noted in imaging or pharmacokinetics between the first and fourth injections. Toxicities included grade 2 urticaria (n = 1), grade 1 vomiting (n = 2), and grade 2 hypertension (n = 1) transiently after infusion at the higher dose.. Given the strong tumor targeting, particularly at the higher dose, the favorable toxicity profile, and the potential for immunomodulatory effects, hu3S193 warrants further investigation in SCLC.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Bone Neoplasms; Brain Neoplasms; Carcinoma, Small Cell; Female; Humans; Indium Radioisotopes; Lewis Blood Group Antigens; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Pilot Projects; Radioimmunotherapy; Time Factors; Tissue Distribution; Treatment Outcome

The blood group antigen Lewis Y is expressed on epithelial tumors of the respiratory, digestive and reproductive system. Despite being regarded as an attractive target for immunotherapy, its function is still not well defined and its prognostic value remains a subject of discussion. Eighty-three paraffin-embedded tissue sections of non-small cell lung cancer (NSCLC) patients in stage I-IIIa, who underwent surgical resection of the primary tumor (73% male; 43% adenocarcinoma), were stained with a new, highly specific monoclonal antibody against Lewis Y (clone A70-C/C8). A positive Lewis Y expression was observed in 51% of patients; adenocarcinomas were favorably stained (67%). Multivariate analysis identified stage I, blood group A or AB and Lewis Y expression on tumor cells to be independent markers for improved survival after tumor resection (p = 0.024, 0.043, 0.003, respectively). In summary, unlike in several previous studies the presence of Lewis Y on tumor cells is a favorable prognostic factor in this cohort of resected NSCLC patients. Coexisting blood group antigen A may be of additional positive prognostic impact. We hypothesize that related blood group antigens both on tumor cells and in peripheral blood may have an underestimated function for progression in resected NSCLC.

Topics: ABO Blood-Group System; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Follow-Up Studies; Humans; Immunoenzyme Techniques; Lewis Blood Group Antigens; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Prognosis; Survival Rate

The immunotoxin BR96 sFv-PE40 is an effective antitumor agent against human breast and lung carcinoma xenografts in rodents. This study was designed to (a) determine the frequency with which canine carcinoma cells express Lewis(y) (Le(y)) antigen, thereby identifying canine carcinoma types suitable for the clinical evaluation of BR96 sFv-PE40, and (b) determine the safety and efficacy of BR96 sFv-PE40 in a canine model of spontaneously occurring cancers for investigation of targeted therapy.. Carcinoma tissue samples were obtained from client-owned dogs presented for medical care. The tissues were assessed for Le(y) antigen expression using immunohistochemical methods. Dogs with tumors expressing Le(y) antigen were offered enrollment in a clinical trial to receive twice-weekly infusions of 4 to 12 mg/m(2) BR96 sFv-PE40. Clinical toxicity and response data were assessed at each treatment.. Twenty-two of 61 carcinomas evaluated were positive for Le(y) expression, including mammary, prostate, lung, and rectal carcinomas, and 12 dogs were enrolled in the clinical trial. The primary side effect was transient emesis. Partial responses or disease stabilization were noted in dogs with inflammatory mammary, bronchogenic, rectal, and tonsillar carcinoma. At least nine of the dogs developed antibodies to the immunotoxin after two to five infusions.. Although development of anti-BR96 sFv-PE40 antibodies limited the long-term effectiveness of this immunotoxin in dogs, rapid clinical responses in several aggressive canine carcinomas suggest the immunotoxin has utility for treatment of certain naturally occurring tumors and that its clinical evaluation for treatment of similar human carcinomas is warranted.

Topics: Animals; Antibodies, Monoclonal; Dogs; Female; Immunotherapy; Immunotoxins; Lewis Blood Group Antigens; Lung Neoplasms; Male; Mammary Neoplasms, Experimental; Mice; Neoplasm Invasiveness; Prostatic Neoplasms; Recombinant Fusion Proteins; Rectal Neoplasms

The chimeric monoclonal antibody cBR96 conjugated to doxorubicin (cBR96-Dox) is selectively internalized by a wide variety of human carcinomas expressing an extended form of Lewis Y antigen (Le(y)). Endocytosis is followed by cleavage and release of free doxorubicin from the endocytic vesicles and subsequent cytotoxicity. Combination studies with standard anti-cancer agents, undertaken to further increase the potency of this targeted therapy, identified significant synergistic anti-tumor activity of cBR96-Dox and either of the taxanes paclitaxel or docetaxel. Treatment with cBR96-Dox 24 hr prior to paclitaxel resulted in a steady increase in the percentage of G(2) tumor cells and corresponding increase in sensitivity to taxanes. Cell cycle analysis indicated the cBR96-delivered doxorubicin was most effective against S-phase cells, yet cells exposed to even subtoxic levels progressed to and arrested in G(2), at a point of high sensitivity to the anti-tubulin agent paclitaxel. The synergy obtained by staged combination of cBR96-Dox and paclitaxel in vitro was reflected in significant anti-tumor efficacy in vivo against xenograft models of human lung and breast tumors that could not be achieved by either agent alone. The staged combination elicited significant or complete regressions of established human Le(y)-positive tumor xenografts using significantly reduced drug levels. Taken together, these data demonstrate a mechanistic approach to the selective elimination of Le(y)-positive tumors by using targeted doxorubicin followed by taxane treatment.

Topics: Adenocarcinoma; Animals; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cell Cycle; Colonic Neoplasms; Docetaxel; Doxorubicin; Drug Screening Assays, Antitumor; Drug Synergism; Humans; Immunotoxins; Inhibitory Concentration 50; Lewis Blood Group Antigens; Lung Neoplasms; Mice; Mice, Nude; Paclitaxel; Taxoids; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

Tumor procoagulant is associated with cancer at advanced stages of malignancy such as infiltration and metastasis. In the present study, we investigated the role of Ley glycolipid in the mechanism of cancer metastasis. Ley glycolipid acts as an important cofactor in the expression of the blood-coagulating activity of cancer cell-derived coagulating activity 1 (CCA-1), which is one of the known tumor procoagulants. Monoclonal antibody (MoAb) FS01, which serves as the Ley-recognizing epitope, inhibits the procoagulant activity of CCA-1 was found to dose-dependently inhibit the procoagulant activity of normal plasma induced by the human lung adenocarcinoma cell line, HAL8, which shows a high level of Ley expression. It did not, however, inhibit the procoagulant activity of the human colon cancer cell line, RPMI4788, which does not express Ley. Administration of FS01 MoAb inhibited lung metastasis of HAL8 cells, but not that of RPMI4788. The absence of antibody-dependent cellular cytotoxicity and complement-mediated cytotoxicity of FS01 MoAb against the HAL8 cell line suggests that the inhibition of HAL8 metastasis by FS01 MoAb derives from the inhibition of blood-coagulating activity of the latter. These findings indicate that Ley glycolipid plays an important role in the mechanism of cancer metastasis via the procoagulant activity of CCA-1.

Topics: Adenocarcinoma; Animals; Antibodies, Monoclonal; Blood Coagulation Factors; Blood Coagulation Tests; Carcinoma, Squamous Cell; Colorectal Neoplasms; Cysteine Endopeptidases; Drug Screening Assays, Antitumor; Flow Cytometry; Glycolipids; Lewis Blood Group Antigens; Lung Neoplasms; Mice; Mice, Nude; Neoplasm Proteins; Tumor Cells, Cultured

The distinction between malignant pleural mesotheliomas and adenocarcinomas, particularly those originating in the lung, is a difficult diagnostic problem that can be facilitated by the use of immunohistochemical markers. In this study, the immunoreactivity of thyroid transcription factor-1 (TTF-1), E-cadherin, BG8, WT1, and CD44S was investigated in 50 epithelial mesotheliomas, and 40 pulmonary and 95 nonpulmonary adenocarcinomas. After analyzing the results, it was concluded that E-cadherin and BG8 are useful markers for distinguishing between epithelial mesotheliomas and adenocarcinomas of various origins, including the lung. Because TTF-1 expression is found almost exclusively in adenocarcinomas of the lung but is absent in mesotheliomas, immunostaining for this marker is particularly useful for distinguishing between these two malignancies. Although WT1 immunostaining may also be useful, its value, as determined in this study, is lower than that reported by other investigators. CD44S immunostaining does not have any practical value in discriminating between epithelial mesothelioma and lung adenocarcinoma.

Topics: Adenocarcinoma; Biomarkers, Tumor; Cadherins; Diagnosis, Differential; DNA-Binding Proteins; Epithelial Cells; Humans; Hyaluronan Receptors; Lewis Blood Group Antigens; Lung Neoplasms; Mesothelioma; Nuclear Proteins; Pleural Neoplasms; Thyroid Nuclear Factor 1; Transcription Factors; WT1 Proteins

The role of Lewis y (Le(y)) antigen expression has been studied extensively in predicting the outcome of various malignancies. We evaluated the expression of Le(y) and its relationship to survival, disease-free survival and other clinicopathologic variables in patients with stage I and II non-small cell lung cancer (NSCLC).. To investigate the prognostic significance of Le(y) antigen expression in a large group of well characterized patients with resected stage I and II NSCLC.. Two hundred and sixty patients with surgically resected stage I (n = 193) and II (n = 67) NSCLC with at least 5-year follow-up were identified.. The median survival for patients with negative expression of Le(y) (< 50% of cells that were positive) was 46 months, whereas for those with positive expression of Le(y) (> or = 50%), the median survival was 54 months (p = 0.99). The disease-free survival for patients with Le(y)(-) expression was 39 months and 34 months for patients with Le(y)(+) expression (p = 0.3).. We found no relationship between loss of blood group antigen A and expression of Le(y). No statistically significant difference was found in survival between positive and negative expression of Le(y) antigen in patients with resected stage I and II NSCLC.

Topics: ABO Blood-Group System; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Female; Humans; Lewis Blood Group Antigens; Lung Neoplasms; Male; Middle Aged; Prognosis; Survival Rate

In contrast to other Lewis blood group-related antigens, Lewis Y antigen (LeY) has not been fully investigated in non-small cell lung cancer.. To assess the significance of LeY expression, 236 patients with completely resected pathologic stage 1-3a were reviewed with immunohistochemical analysis.. LeY expression was positive in 179 patients (75.8%). In poorly differentiated cancer, percentage of LeY-positive patients was lower than in moderately to well-differentiated cancer (67.2% versus 81.2%, p = 0.028). Five-year survival rate of LeY-positive patients was 78.2%, significantly higher than that of LeY-negative patients (59.7%, p = 0.001). Combined with p53 status, differences in survival proved to be marked; 5-year survival rate of patients with positive LeY expression and without aberrant p53 expression, was as high as 83.3%, whereas that of patients with negative LeY expression and with aberrant p53 expression was only 38.4% (p < 0.001). Multivariate analysis confirmed that LeY expression was a significant independent factor to predict better survival.. LeY expression is a significant prognostic factor related to grade of cancer differentiation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Carcinoma, Non-Small-Cell Lung; Female; Humans; Immunohistochemistry; Lewis Blood Group Antigens; Lung Neoplasms; Male; Middle Aged; Multivariate Analysis; Prognosis; Tumor Suppressor Protein p53

The most common clinical form of lung cancer is a disseminated disease with distant metastases; several years of cancer progression precede presentation, and this ultimately limits the efficacy of curative therapy. In this immunohistochemical study, we examined a mucinous adenocarcinoma cell line, maintained by xenogeneic transplantation, and a spontaneous metastatic variant which produces distant tumors (in liver, spleen and kidney). The aim was to investigate possible parameters which characterize the metastatic process. Histopathological comparison between the two subcutaneous transplanted tumor lines showed that both lines presented a similar cellular morphology, a different pattern of cellular growth and an increased vascularization in the metastatic line with respect to its parent. All the tumor sections expressed differential immune reactivity with monoclonal antibodies against Lewis y (MAb C14), sialyl-Lewis x (MAb SNH3) and Lewis x (MAb FH2) determinants. Neither expressed MUC 1 mucins detectable with monoclonal antibodies reactive with the mucin protein core (MAbs C595 and SM3) nor was carcinoembryonic antigen (MAb C365) expressed. Neoplastic cells were reactive with an anti-pan cytokeratin monoclonal antibody confirming their epithelial histogenesis. Our findings have been evaluated with respect to defining metastatic phenotypes in lung cancer by examination of distinct histopathological and immunological parameters.

Topics: Adenocarcinoma, Mucinous; Animals; Antibodies, Monoclonal; Apoptosis; Biomarkers, Tumor; Carcinoembryonic Antigen; Cell Nucleus; Cytoplasm; Gangliosides; Humans; Image Processing, Computer-Assisted; Immunoenzyme Techniques; Injections, Subcutaneous; Kidney Neoplasms; Lewis Blood Group Antigens; Lewis X Antigen; Liver Neoplasms, Experimental; Lung Neoplasms; Mice; Mice, Nude; Mucin-1; Mucins; Neoplasm Proteins; Neoplasm Transplantation; Neoplastic Stem Cells; Oligopeptides; Peptide Fragments; Phenotype; Sialyl Lewis X Antigen; Splenic Neoplasms; Transplantation, Heterologous; Tumor Cells, Cultured

We have developed a highly specific gene transfer method for adenocarcinoma using a monoclonal antibody against tumor-specific antigen coupled with a plasmid containing the carcinoembryonic antigen (CEA)-specific promoter. The chimeric CEA promoter (CC promoter), which contained an enhancer from the immediate early gene of cytomegalovirus and the CEA promoter, achieved 4- to 5-fold higher transgene expression in CEA-producing cells than the original CEA promoter while maintaining CEA specificity. Furthermore, a complex of a monoclonal antibody against Lewis Y antigen (LYA), the CC promoter-containing plasmid and cationic liposomes (DOTAP) achieved specific gene expression in CEA-producing and LYA-positive adenocarcinoma cell lines that was 200-fold more efficient than in CEA-non-producing and LYA-negative cell lines during a short in vitro incubation. This strategy may be applicable for clinical gene therapy.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Neoplasm; Carcinoembryonic Antigen; Colorectal Neoplasms; Combined Modality Therapy; Gene Transfer Techniques; Genetic Therapy; Humans; Lewis Blood Group Antigens; Liposomes; Lung Neoplasms; Organ Specificity; Promoter Regions, Genetic; Tumor Cells, Cultured

Topics: Adenocarcinoma; Adjuvants, Immunologic; Antibodies, Monoclonal; Antibody-Dependent Cell Cytotoxicity; Complement Inactivator Proteins; Humans; Lewis Blood Group Antigens; Lung Neoplasms; Tumor Cells, Cultured

Complement-dependent cytotoxicity (CDC) mediated by a chimeric anti-Lewis Y monoclonal antibody (cH18A; human IgG1) was investigated in this study. Human lung adenocarcinoma cell lines (PC7, PC9, and PC14) were used as the target cells. PC7 and PC9 cells, expressed Lewis Y antigen and were lysed by cH18A as effectively as by the parent mouse anti-Lewis Y antibodies (mH18A) in a concentration-dependent manner. PC14 cells did not express Lewis Y antigen and were not lysed by either cH18A or mH18A. cH18A mediated CDC activity against PC7 and PC9 cells was enhanced by the combined use of monoclonal antibodies directed against CD46(MCP), CD55(DAF), and CD59. These molecules are complement-regulatory proteins which protect host cells from CDC. PC7 and PC9 cells, showed high levels of surface expression of these proteins, PC7 cells were more susceptible to cH18A-mediated CDC than PC9 cells. Use of multiple blocking antibodies to the complement-regulatory proteins produced more enhancement of cH18A-mediated CDC than a single antibody. Moreover, expression of CD55 and CD59 by PC7 and PC9 cells was decreased after treatment with PI-PLC, resulting in increased susceptibility to cH18A-mediated CDC. Although the reason is unknown, PC7 cells became more susceptible to CDC than PC9 cells after PI-PLC treatment even in the absence of cH18A. These data suggest that chimeric monoclonal antibodies can be used to induce CDC against lung adenocarcinoma, and that such CDC is potentiated by a variety of antibodies blocking compliment-regulatory proteins on the tumour cell surface.

Topics: Adenocarcinoma; Animals; Antibodies, Monoclonal; Antibody-Dependent Cell Cytotoxicity; Antigens, CD; CD55 Antigens; CD59 Antigens; Cell Line, Transformed; Humans; Lewis Blood Group Antigens; Lung Neoplasms; Membrane Cofactor Protein; Membrane Glycoproteins; Mice