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M I Colnaghi

Publications and source records attributed to M I Colnaghi.

At least 91 records · Page 5Linked to original sources
PubMed1994

Relevance of antibody valency in EGF receptor modulation.

Binding characteristics of a monovalent bispecific monoclonal antibody (bsMoAb), which recognizes both epidermal growth factor receptor (EGF-R) and drug doxorubicin (DXR) were compared with those of the parental bivalent MoAb directed against the EGF-R binding site. Scatchard analysis indicated that both MoAbs bound to EGF-R-overexpressing A431 cells with the same affinity. In tracer amounts, both MoAbs also displayed the same capacity to be internalized after binding to the cell surface. However, when the MoAbs were used at saturating concentrations, down-modulation of the receptor was greater with the bivalent MoAb. The bivalent MoAb also inhibited proliferation of A431 cells both in vitro and in vivo whereas the bsMoAb was inhibitory only in vivo. These data suggest that MoAb bivalency is required for EGF-R down-modulation and in vitro cell growth inhibition.

Animals↗
PubMed1993

Antibody response against the c-erbB-2 oncoprotein in breast carcinoma patients.

Indirect immunofluorescence analysis of sera from breast carcinoma patients whose tumors were characterized for overexpression of the c-erbB-2 oncoprotein (p185HER2) and for lympho-plasma cell infiltration, revealed no circulating antibodies specifically directed against the p185HER2 molecule in the 20 samples tested, whereas supernatants of B-cell clones, derived from Epstein-Barr virus-transformed peripheral blood lymphocytes from 10 of these patients, contained such antibodies in 6 of the 7 c-erbB-2- and lympho-plasma cell infiltration-positive cases. The antibodies contained in two of the positive supernatants immunoprecipitated a M(r) 185,000 molecule from oncoprotein-positive cell extracts that was identified as the oncoprotein in sequential immunoprecipitation experiments with anti-p185HER2 monoclonal antibodies. No cells producing antibodies with a similar reactivity were obtained from Epstein-Barr virus-transformed peripheral blood lymphocytes from breast carcinoma patients with p185HER2-negative tumors or from healthy donors. These data prove the existence of an antibody response specifically directed against the p185HER2 oncoprotein in breast carcinoma patients that may represent an important effector mechanism in the control of c-erbB-2-overexpressing tumors.

Antibodies↗
PubMed1993

Targeting of T lymphocytes against EGF-receptor+ tumor cells by bispecific monoclonal antibodies: requirement of CD3 molecule cross-linking for T-cell activation.

Targeting of T lymphocytes against epidermal growth-factor-receptor (EGF-R)+ tumor cells was achieved by constructing a hybrid hybridoma which secretes an anti-EGF-R/anti-CD3 bispecific monoclonal antibody (biMAb) of hybrid isotype (IgG1/IgG2a). Purification of biMAb molecules from parental anti-EGF-R and anti-CD3 MAbs was performed by protein-A chromatography. The purified biMAb was able to trigger the lysis of EGF-R+ tumor cell lines (A431, IGROV-1, MDA-468 and U-87) and of NIH-3T3 transfectants expressing human EGF-R by cytolytic T lymphocytes, but it was ineffective in the case of EGF-R-negative tumor targets. Normal EGF-R+ cells (keratinocytes and endometrial cells) were also susceptible to biMAb-targeted cytolysis. However, the amount of biMAb required to induce half-maximal cytolysis of tumor cells over-expressing the EGF-R molecule (A431) was considerably lower than that required to induce lysis of EGF-R+ tumor or normal cells which express EGF-R at considerably lower density. The ability of such biMAbs to deliver activation signals to T cells was evaluated by Ca++ mobilization and lymphokine production experiments. The soluble anti-EGF-R/anti-CD3 biMAb failed to induce intracellular Ca++ increases, which occurred only after cross-linking induced by an anti-mouse IgG antibody. Secretion of lymphokines (IFN-gamma, TNF-alpha and GM-CSF) was induced by contact of the biMAb-coated effector cells with the relevant tumor target, whereas the soluble biMAb was virtually ineffective. In addition, biMAb-coated effector cells retained the ability to recognize and to lyse EGF-R+ tumor cells for a prolonged period of time. Our data indicate that activation of effector cells targeted by biMAbs can only occur at the tumor site, where cross-linking of surface CD3 molecules is induced by contact with the tumor cells.

Antibodies, Bispecific↗
PubMed1993

Gene transfection and expression of the ovarian carcinoma marker folate binding protein on NIH/3T3 cells increases cell growth in vitro and in vivo.

The glycoprotein gp38 is overexpressed in 90% of ovarian carcinomas and recognized by monoclonal antibodies MOv18 and MOv19. This molecule is a high affinity folate binding protein (FBP) and a potential marker for ovarian carcinoma. We have developed a model to investigate the biochemical and biological properties of this folate receptor by transfecting NIH/3T3 cells, which do not endogenously express FBP, with a vector containing the complementary DNA for the gp38 cloned from the ovarian carcinoma cell line IGROV1. The FBP expressed shows features identical to those of the protein produced by IGROV1 cell. The FBP is expressed on the cell membrane in a glycosylphosphatidylinositol-linked form, since it is released by treatment with phosphatidylinositol-specific phospholipase C, and is shed into the culture medium of the NIH/3T3 transfectants. Immunoblot analysis with MAbs MOv18 and MOv19 showed that both the glycosylphosphatidylinositol-linked and the soluble FBP migrate at the same apparent molecular weight as the respective IGROV1 proteins. The FBP-transfected NIH/3T3 cells bound folic acid and internalized about 30-fold more folic acid than mock-transfected cells. Growth analysis revealed that FBP-transfected NIH/3T3 cells like IGROV1 maintained their growth rate after 10 days of culture in medium containing physiological or low folate concentration, and tumors arising after transplanting FBP-tNIH/3T3 cells in nude mice were 3-fold heavier than those arising after transplantation of non-FBP-expressing NIH/3T3 cells. These results suggest a correlation between human ovarian carcinoma growth and FBP overexpression.

3T3 Cells↗
PubMed1993

Effect of hydrostatic pressure and cholesterol depletion on the expression of a tumor-associated antigen.

The molecular events related to the expression of three tumor-associated epitopes, Ca-MOv17, Ca-MOv18 and Ca-MOv19 have been addressed. The epitopes are carried by a 38-kDa glycoprotein (gp38), recently cloned and identified as a human folate-binding protein. They were found to be coexpressed on the surface of the ovarian carcinoma cell line OVCA432, while they are not coordinately expressed on other adenocarcinoma cell lines (IGROV1, HT-29). This lack of coexpression was investigated from a molecular point of view. We studied three carcinoma cell lines, characterized by a different reactivity with the three relevant monoclonal antibodies MOv17, MOv18 and MOv19. The epitope expression was examined after modifying the membrane properties by using hydrostatic pressure and/or the variation of cholesterol content. Measurement of the expression after cell labelling by mAbs was performed by indirect immunofluorescence, using both fluorescence microscopy and flow cytometry. At variance with HT-29 cells, treatment of ovarian carcinoma IGROV1 cells with hydrostatic pressure failed to exert any effect. On IGROV1, instead, cholesterol depletion affected the expression Ca-MOv17, increasing, in the indirect immunofluorescence tests, the proportion of positive cells from 0 to 66 +/- 9%. Moreover, restoring the cholesterol content of the plasma membrane did not reverse the induced epitope expression. In parallel, immunoprecipitation experiments confirmed that, on IGROV1 surface, gp38 was recognized by all three mAbs. The data presented suggest that in IGROV1 cells the selective lacking of the epitope expression is related to the physical state of the plasma membrane. An explanation is provided by the model of membrane microdomains in which epitope expression may be influenced by the cholesterol level of different plasma membrane regions.

Adenocarcinoma↗
PubMed1993

Use of a pool of monoclonal antibodies in diagnosing cells from serous cavities.

AIMS AND BACKGROUND: The usefulness of monoclonal antibodies that recognize markers of neoplastic lesions in complementing conventional cytology was evaluated by the avidin-biotin-peroxidase complex, indirect immunoperoxidase technique. METHODS: In order to enhance the sensitivity of the traditional method, a pool of seven combined monoclonal antibodies (Pool C7), which reacts specifically with cells of epithelial origin and is able to distinguish between mesothelial and malignant cells, was tested on cytologic smears of 262 serous effusions. The effusions were benign or neoplastic, mainly from breast, ovary and lung cancers. RESULTS: Immunocytochemical method showed an 100% specificity and 100% of predictivity whereas the sensitivity was 98%, 96% and 95% for breast ovarian and lung carcinomas, respectively. CONCLUSIONS: The results demonstrated that the pool when used together with conventional methods, is useful in analysis of serous effusions in diagnostic investigations.

Antibodies, Monoclonal↗
PubMed1993

Polarization of the alpha 6 beta 4 integrin in ovarian carcinomas.

By immunizing a BALB/c mouse with a human ovary-carcinoma cell line (IGROV1), grown intraperitoneally in nude mice, a monoclonal antibody (MAb), designated MAR6, was produced and characterized. Immunofluorescence on the immunizing cell line showed a specific labelling by MAR6 at the cell-to-cell contact points. In addition, MAR6 was found to immunoprecipitate the alpha 6 beta 4 integrin complex. Competition tests with MAbs anti-alpha 6, anti-beta 4, anti-beta 1 sub-units demonstrated that the recognized sub-unit is alpha 6. Indirect immunofluorescence on various cell lines gave MAR6 as positive only on alpha 6-positive lines (IGROV1, OVCAR3, SW626, SKOV3, ME4405, Calu3, N592, MDA468, A431 and HT29). Moreover, on IGROV1 and OVCAR3 ovary-carcinoma cells, which normally grow either adhering to the culture flask or forming clumps in suspension in the medium, MAR6 selectively stained the connection points between the cells in clumps, where, in the same position, the presence of the beta 4 sub-unit, laminin and fibronectin was detected. On the contrary, the beta 1 sub-unit was distributed over the whole cell membrane. The same pattern of labelling by these MAbs was observed in 2 cases of ovarian-carcinoma cells present in ascitic fluids obtained from patients. Immunoperoxidase tests performed on cryosections of various normal tissues showed specific reactivity of MAR6 on basal or basolateral membranes of epithelial cells. On cryosections of ovarian tumors, MAR6 reactivity correlated with the degree of tumor differentiation. Indeed, in benign and well-differentiated tumors, a strong basal or basolateral labelling only of cells surrounding the neoplastic nodules was found. On the contrary, on undifferentiated tumors the inner part of the tumor nodules was also progressively labelled, whereas the staining on the border was weak and discontinuous as a result of the alpha 6 sub-unit dispersion on the tumor cell surface.

Antibodies, Monoclonal↗
PubMed1993

Prognostic significance of the 67-kilodalton laminin receptor expression in human breast carcinomas.

BACKGROUND: The 67-kd laminin receptor is a cell-surface protein that binds laminin with high affinity. In vitro studies suggest that this protein is involved in the progression of human tumors to invasive cancers (metastasis), but there have been few in vivo studies. Identification of such proteins would allow development of therapies aimed at interfering with their mechanisms of action. PURPOSE: This large retrospective study was designed to investigate the association of expression of this laminin receptor molecule with established prognostic factors and overall survival in breast carcinoma patients. METHODS: We immunohistochemically stained archival paraffin-embedded sections of 1160 primary breast carcinomas, using an immunoperoxidase technique and the MLuC5 monoclonal antibody, which is specific for the 67-kd laminin receptor. Specimens were obtained from consecutive surgeries performed from January 1968 through December 1971. Patients with negative lymph nodes or involved regional nodes had been treated with surgery alone; those with positive axillary nodes had received surgery and radiotherapy. No chemotherapy had been administered until disease recurrence. The statistical analysis was carried out using the logrank method for the survival curves and the actuarial life table to calculate survival rates according to the different prognostic variables. RESULTS: We found statistically significant associations between laminin receptor expression and young age (P < .001), premenopausal status (P = .001), positive axillary lymph nodes (P = .01), peritumoral lymphatic invasion (P = .02), and the diameter of the tumor (P = .05). Moreover, the association of expression of the receptor protein with poor prognosis, as indicated by survival curves, was statistically significant (P < .01). For patients with receptor-negative tumors, the survival rate was 50% at 20 years; for those with receptor-positive tumors, the survival rate was 50% at 13 years. Multivariate analysis showed the laminin receptor to be an independent prognostic factor (P = .005), indicating its predictive value in relation to overall survival. CONCLUSIONS: Our data suggest that the 67-kd laminin receptor is associated with the metastatic process. IMPLICATIONS: These preliminary findings also suggest that hormones may have a regulatory role in the in vivo expression of the 67-kd laminin receptor, which supports the hypothesis that hormone therapy might inhibit expression of the receptor. Studies of expression of this receptor in tumors of patients with extremely different sex hormone levels (e.g., men and pregnant women) are in progress.

Antibodies, Monoclonal↗
PubMed1993

Isolation and biochemical characterization of the soluble and membrane forms of folate binding protein expressed in the ovarian carcinoma cell line IGROV1.

The human ovarian carcinoma cell line, IGROV1, produces two forms of folate binding protein (FBP), the membrane form that is anchored to the cell surface by a glycosylphosphatidylinositol tail and the soluble form that is shed into the tissue culture medium. Both forms are recognized by the monoclonal antibodies MOv18 and MOv19. Here we describe their purification and biochemical characterization. The purified soluble protein appeared as a single band with an apparent Mr of 36 kDa after SDS-PAGE, whereas the membrane form appeared as a single band with an apparent Mr of 38 kDa. The size difference between the two forms of FBP was confirmed by gel filtration of both the native and the N-glycanase-treated proteins. Both purified proteins had equal capacity to bind folic acid. The immunological cross-reactivity and the folic acid binding capability of the FBPs extracted from IGROV1 gave more evidence of the possible existence of a precursor-product relationship between them.

Carrier Proteins↗
PubMed1993

A critical comparison of three internalization assays applied to the evaluation of a given mAb as a toxin-carrier candidate.

In the attempt to define a strategy for screening new monoclonal antibodies (mAb) that could be appropriate for clinical application in oncology, we evaluated the suitability of three methods: a direct internalization assay (DIA), an indirect internalization assay (IIA) and an indirect cytotoxicity assay (ICA), by applying them to already selected mAb. The latter were directed against three antigenic systems [38-kDa glycoprotein (gp38), epidermal growth factor receptor, and the neu oncogene product], which, according to their tumor selectivity, could be considered suitable for mAb-guided therapy. The dose-dependent and time-dependent binding, as well as the low intra-assay variability, demonstrated the reliability of the three tests. However, a certain degree of inter-assay variability was observed in each one, the highest value being that found when IIA was applied. Furthermore, the degree of variability, as well as the predictability, seemed to be more related to the mAb/antigen (Ag) combination used rather than to the test applied. From the overall data we suggest a procedure to be applied for screening purposes. As a first approach applied to the raw material, ICA is only suitable for screening in the case of an already selected toxin whereas IIA may be helpful to eliminate the true negative mAb. After purification of the relevant mAb a repeated analysis using DIA could allow the selection of true internalizing mAb. However, this second screening should be followed by a further analysis of the fate of the Ag-Ab complex after internalization.

Antibodies, Monoclonal↗
PubMed1993

Antibody-induced activation of p185HER2 in the human lung adenocarcinoma cell line Calu-3 requires bivalency.

In the present study we utilized two previously described monoclonal antibodies (mAb), and their respective Fab portions, directed against the extracellular domain of p185HER2, a transmembrane glycoprotein with intrinsic tyrosine kinase activity coded by the HER2/neu oncogene, to study the mechanism of mAb-induced receptor internalization and phosphorylation. Fluorescence scan analysis and direct binding of radiolabelled mAb and their Fab fragments showed that entire MGR2 and MGR3 mAb were reactive with similar binding affinity on two cell lines (Calu-3 and Sk-Br-3) overexpressing the p185HER2 receptor, and unreactive on unrelated cells. The corresponding Fab fragments were positive on the related cells, but bound with diminished intensity and affinity. Entire MGR2 and MGR3 induced internalization in both Calu-3 and Sk-Br-3 cells, whereas their Fab portions were not internalized. When the bivalency of the MGR2 Fab fragment was artificially reconstituted by incubation with rabbit anti-(mouse IgG), internalization was obtained. Monovalent binding of the entire labelled antibodies, obtained in the presence of a saturating amont of unlabelled antibody, decreased both the rate and the final amount of internalized antibody. Metabolic labelling and immunoblotting experiments showed that incubation with entire MGR3 amplified the basal phosphorylation of the p185HER2 receptor in Calu-3 and Sk-Br-3 cells, whereas MGR3 Fab decreased the signal. Taken together, our data indicate that antibody-mediated activation of p185HER2 in Calu-3 and Sk-Br-3 cells occurs through the dimerization of receptor molecules and that bivalency of the activating antibody is mandatory for induction of internalization and phosphorylation of the receptor. Our data support an allosteric model of activation for the p185HER2 receptor.

Adenocarcinoma↗
PubMed1993

Prognostic significance of the CaMBr1 antigen on breast carcinoma: relevance of the type of recognised glycoconjugate.

An extensive study of the expression of the blood group-related antigen CaMBr1 has been performed by immunohistochemistry, immunoblotting and high performance thin layer chromatography both on frozen and paraffin-embedded (paraffin) samples from normal and neoplastic breast tissues. The glycolipid antigenic fraction (from frozen samples) was preferentially expressed on functioning breast epithelium. In a prospective series of 143 breast cancer cases CaMBr1 expression was associate, on frozen sections, with the transferrin receptor (P = 0.01), the positivity with oestrogen receptor immunochemical assay (P = 0.06), premenopausal status (P = 0.06) and node negativity (P = 0.07). Non-significant correlation with longer disease-free survival (DFS) was observed. In a retrospective series of 862 cases on paraffin sections the glycoproteic antigenic fraction was significantly associated with premenopausal status (P < 0.05) and lobular histotype (P < 0.01), but failed to predict survival, although a trend for longer DFS was observed for positive cases.

Antigens, Neoplasm↗
PubMed1993

Study of the expression and function of the tumour-associated antigen CaMBr1 in small cell lung carcinomas.

The expression of the epithelial antigen recognised by the MBr1 monoclonal antibody (CaMBr1) was studied on 161 small cell lung carcinoma (SCLC) biopsies. A correlation between the marker expression and the overall survival of the patients was found. To investigate the possible role of CaMBr1 in tumour aggressiveness, the in vivo and in vitro growth capabilities of different SCLC cell lines, in relation to the antigen expression, were analysed. The CaMBr1-positive cell lines displayed a higher growth potential in comparison to CaMBr1-negative cells. The biochemical nature of CaMBr1 was analysed in terms of enzyme sensitivity, molecular weight and comparison with other glycoproteins expressed by SCLC cells. The results indicated the trypsin sensitivity of the molecule, and sialic acid hiding of the CaMBr1 epitope. The increase of MBr1 reactivity after neuraminidase treatment suggests that the CaMBr1 epitope expressed in the SCLC cell line is carried by a sialoglycoprotein.

Animals↗
PubMed1993

Evolution of the therapeutic use of new monoclonal antibodies.

Peptide or carbohydrate epitopes resulting from aberrant glycosylation, receptors for growth, and differentiation signals have recently been reexamined as candidates for monoclonal antibody-guided therapy. Microdistribution studies have demonstrated the limited penetration of radiolabeled antibodies in tumors. Increased tumor capillary permeability has been obtained by pretreatment with cytokines or by exploitation of monoclonal antibodies against tumor endothelial cells. The use of monoclonal antibodies for combined therapies based on different rationales (multiple monoclonal antibodies, monoclonal antibodies plus cytokines, and monoclonal antibodies plus drugs) is a recent development, and the retargeting of effector cells using hybrid monoclonal antibodies can be considered an extension of this approach. A major driving force in the field of immunotoxins today is represented by progress in protein engineering. Genes encoding various toxins have been cloned, and novel molecules with more desirable biologic properties have been produced. Also, genetic engineering techniques help in overcoming the major limitation in the clinical use of rodent monoclonal antibodies, ie, human antiimmunoglobulin response.

Animals↗
PubMed1993

Alteration of laminin production in small-cell lung carcinoma: possible correlation with the absence of the basement membrane.

Basement membranes are frequently absent in small-cell lung cancer (SCLC). To study this phenomenon, the production of laminin by SCLC cells, both in vitro and in vivo, has been investigated and compared with the laminin production by lung carcinomas of other histotypes (non-SCLC, NSCLC). Immunoradiometric and immunoperoxidase tests, respectively, carried out on culture supernatants and cells using antilaminin rabbit antiserum, revealed that in 1 (H446) out of 8 SCLC cell lines tested and in the NSCLC line Calu3, laminin was detectable both in the culture medium and in the cytoplasm of the cells. After treatment of an SCLC-negative cell line (N592) with monensin, a molecule which inhibits protein secretion, laminin became detectable in the cytoplasm. Similar results were obtained by FACS analysis on cells permeabilized with saponin. Northern analysis indicated that the laminin B1 gene was transcribed. The level of mRNA for the B1 laminin subunit in the N592 cells was twice and 4 times higher than that found in the laminin-secreting Calu3 and H446 cell lines. The production of laminin in SCLC and NSCLC surgically resected samples using immunoperoxidase staining of cryostatic sections was also investigated. The results indicate that 85% of the NSCLC cases tested showed diffuse staining in the cytoplasm of the tumor cells and strong staining at the basement membrane level, whereas a similar staining was only found in 15% of the SCLC cases tested. The treatment of SCLC cells with differentiating agents in vitro has been shown to induce the adhesion of these cells. In fact, n-butyric acid induced the disaggregation of floating-clump cells and single-cell adhesion in the N592 line, whereas after treatment with retinoids the clumps of the N592 cells were still present, but 30% of these were found to adhere to the plate. However, no increase in the laminin production was found in the cytoplasmic or culture medium under these conditions.

Adenocarcinoma↗
PubMed1993

The extracellular domain of the c-erbB-2 oncoprotein is released from tumor cells by proteolytic cleavage.

A molecule that is immunologically related to the c-erbB-2 oncogene product (p185HER2/neu) was detected in the conditioned culture medium from neu-overexpressing tumor cell lines and in sera of advanced-stage breast carcinoma patients. Using a sensitive (in the range of 0.5 ng ml-1) double-determinant radioimmunoassay (DDIRMA) with two monoclonal antibodies (MAbs) directed against the neu extracellular domain (ECD), soluble oncoproteins were detected in supernatants from several neu-positive tumor cell lines, independent of the levels of membrane p185HER2 expression. The molecule detected did not react with a MAb directed against an intracytoplasmic epitope of the p185HER2. Western blot analysis of the concentrated supernatant revealed a protein of approximately 110 kDa molecular mass, which closely matches the predicted size of the glycosylated p185HER2 ECD. Immunoprecipitation of culture supernatant from cell surface-radioiodinated cells confirmed the 110 kDa molecular mass of the glycosylated shed protein, which migrated to 86 kDa after deglycosylation. Proteolytic cleavage of the p185HER2 molecule was demonstrated in release assays carried out with protease inhibitors. The combined use of leupeptin and EDTA completely inhibited release of the molecule. Analysis of sera from breast carcinoma patients and healthy donors by DDIRMA revealed the presence of soluble neu in 15% of pathologic sera but none of the normal sera. A good correlation was found between neu-overexpression in the primary tumor and the soluble marker in serum of patients with advanced disease; sera of early-stage patients were always negative, independent of neu-overexpression in the tumor. These results suggest the usefulness of soluble neu as an indicator of tumor aggressiveness but not as a diagnostic marker of breast cancer.

Biomarkers, Tumor↗
PubMed1993

Use of anti-CD3 and anti-CD16 bispecific monoclonal antibodies for the targeting of T and NK cells against tumor cells.

To target T lymphocytes against EGF-R+ tumors, we constructed anti-CD3/anti-EGF-R bimAbs either by the generation of a hybrid hybridoma (quadroma) or by a chemical cross-linking method. Analysis of the in vitro functional activity of these two different constructs indicated that the quadroma-secreted bimAb was more efficient in targeting the CD3+8+ clones against EGF-R+ target cells with respect to the bimAb produced by chemical method. In addition, the quadroma-produced bimAb is able to induce cytolysis of EGF-R+ tumor cell lines of PHA-induced lymphoblasts that had been expanded in IL-2-containing medium, whereas tumor cells lacking expression of EGF-R were not lysed. Resting PBL targeted by the bimAb did not display significant cytotoxicity against the relevant tumor. An anti-CD16 hybridoma (IgG1) was fused with an anti-folate-binding protein hybrid (IgG2a) to construct bimAbs to target NK cells against NK-resistant ovarian carcinomas. The hybrid IgG1/IgG2a bimAb triggered the specific lysis of relevant target cells by resting NK cells, but it was ineffective when CD8+TCR alpha/beta+ cultured cell populations were used as effectors. Only marginal increases of cytolytic activity could be induced by the bimAb when IL-2-activated PBL (i.e., LAK cells) were used as effectors due to the high cytolytic activity of these cells against the relevant tumors in the absence of bimAb. The possible use of anti-CD16 or anti-CD3 bimAbs for the development of different cellular immunotherapy strategies against cancer is discussed.

Antibodies, Bispecific↗