Biomedical subjects

S Ferrone

Publications and source records attributed to S Ferrone.

At least 145 records · Page 8Linked to original sources

PubMed1992

Diversity of anti-HLA-DR antibodies elicited by distinct anti-idiotypic monoclonal antibodies recognizing idiotopes co-expressed by the immunizing monoclonal antibody.

Analysis at the clonal level of the idiotypic network has identified differences in fine specificity between antigen-binding anti-anti-idiotypic (anti-anti-id) monoclonal antibody (mAb) and the original mAb as well as among antigen-binding anti-anti-idiotypic (anti-id) mAb. However, the diversity of humoral immune responses elicited by anti-id mAb recognizing idiotopes co-expressed on the immunizing mAb has not been analysed. Since this information may contribute to our understanding of the role of anti-id antibodies in the generation of diversity in the course of an immune response, we have compared the fine specificity and idiotype profile of two subsets of anti-HLA-DR mAb generated with the anti-id mAb F5-444 and F5-830. The latter mAb recognize idiotopes co-expressed in the antigen-combining site of the immunizing anti-HLA-DR1,4,w14,w8,9 mAb AC1.59. These investigations showed that: (1) the two subsets of anti-HLA-DR mAb overlap only partially in their reactivity patterns with HLA-DR+ cells; (2) both subsets of anti-HLA-DR mAb recognize spatially close epitopes; (3) each subset of anti-HLA-DR mAb has unique reactivity patterns with soluble HLA-DRw16 and DRw17 antigens; and (4) each subset of anti-anti-id mAb displays a distinct idiotype profile. The subtle differences in the fine specificity and idiotype profile of the two subsets of anti-HLA-DR mAb suggest that anti-id antibodies may play a role in the generation of diversity in the course of a humoral immune response.

Antibodies, Anti-Idiotypic↗

PubMed1992

Immunotherapeutic approaches with monoclonal antibodies to immunological diseases.

The molecular events triggered by the interaction of the immune system with an antigen and leading to an immune response have been characterized in recent years. This information has provided the background to develop immunotherapeutic approaches to allograft rejection and to autoimmune diseases utilizing monoclonal antibodies to molecules which play a role in the immune response. The clinical trials performed thus far are described. The significance of the results obtained in these trials and the future potential developments are discussed.

Antibodies, Monoclonal↗

PubMed1991

Human high molecular weight-melanoma associated antigen mimicry by an anti-idiotypic antibody: characterization of the immunogenicity and the immune response to the mouse monoclonal antibody IMel-1.

The mouse anti-idiotype (anti-id) monoclonal antibody (mAb) IMel-1 recognizes an idiotope in the antigen combining site of the immunizing anti-human high molecular weight melanoma-associated antigen (HMW-MAA) mAb 225.28. The mAb IMel-1 is able to induce an immune response against self cross-reacting HMW-MAA in rabbits that express HMW-MAA in normal tissues. Most of the rabbit anti-anti-id antibodies recognize a spatially distant determinant(s) from that defined by anti-HMW-MAA mAb 225.28. The immunogenicity of mAb IMel-1 is enhanced by its administration with the muramyl dipeptide-derived adjuvant. Anti-HMW-MAA antibodies were not detected in sera from rabbits immunized with HMW-MAA bearing cultured human melanoma cells. The differential immunogenicity of mAb IMel-1 and cell membrane bound HMW-MAA may account for the ability of anti-id mAb to induce anti-HMW-MAA immunity in patients who have not mounted such a response to HMW-MAA present in their lesions. Rabbit anti-HMW-MAA antibodies induced by anti-id mAb IMel-1 inhibited interactions of melanoma cells with elements of extracellular matrix. This may represent an additional mechanism by which anti-HMW-MAA immunity may affect the biology of melanoma cells in patients with melanoma immunized with anti-id mAb IMel-1.

Animals↗

PubMed1991

Improvement by affinity chromatography on antiidiotypic monoclonal antibodies (MAbs) of immunoreactivity and in vivo targeting of radiolabelled anti-HMW-MAA MAb TP61.5 in nude mice bearing human melanoma lesions.

The human high-molecular-weight melanoma-associated antigen (HMW-MAA) represents a useful marker for immunoscintigraphy in patients with melanoma. Since injection of a radiolabelled anti-HMW-MAA monoclonal antibody (MAb) visualizes only about 60% of melanoma lesions, approaches are being developed to increase the sensitivity of immunoscintigraphy. One of them aims at improving the immunoreactivity of radiolabelled anti-HMW-MAA MAbs, since this approach may improve the targeting of radiolabelled MAbs to melanoma lesions. We have previously shown that affinity chromatography on insolubilized anti-idiotypic MAbs is a useful method for purifying immunoreactive anti-HMW-MAA MAb TP61.5 from 125I-labelled MAb preparations and that not all the anti-idiotypic MAbs are useful for this purpose. Since the increasing number of available anti-idiotypic MAbs is likely to facilitate the application of this procedure in many antigenic systems, we have now tested criteria to select anti-idiotypic MAbs suitable for the purification procedure. Furthermore, we have investigated the effect of the increase in immunoreactivity of 125I-MAb TP61.5 on its in vivo targeting to human melanoma lesions transplanted into nude mice. Among the 3 anti-idiotypic MAbs tested, the most effective in purifying immunoreactive MAb TP61.5 molecules following radiolabelling is MAb TK7-110, with which 125I-MAb TP61.5 displays an immunoreactivity similar to that displayed with melanoma cells. This parameter may represent a useful criterion to identify anti-idiotypic MAbs suitable for the purification procedure, if the present results are confirmed with a large number of anti-idiotypic MAbs in different antigenic systems. We have also shown that an incubation time for up to 4 hr of 125I-MAb TP61.5 with insolubilized MAb TK7-110 is the most effective in increasing immunoreactivity and in recovering immunoreactive MAb applied to the affinity matrix. The increase in the immunoreactive fraction of 125I-MAb TP61.5 significantly increases its specific localization in human melanoma lesions transplanted into nude mice. These results suggest that purification of radiolabelled immunoreactive anti-HMW-MAA MAb TP61.5 by affinity chromatography using anti-idiotypic MAb TK7-110 represents a useful approach to increasing the sensitivity of immunoscintigraphy in patients with melanoma.

Animals↗

PubMed1991

T-cell malignancies with mature phenotypes: altered cell cycle regulation by HLA class I molecules.

Soluble anti-HLA class I monoclonal antibodies (MoAbs) modulate normal T-lymphocyte proliferation induced via the CD3/Ti and the CD2 pathway, but do not induce proliferation of normal T lymphocytes in the absence of additional mitogenic stimuli. In this report, we show that anti-HLA class I MoAbs induce DNA synthesis in peripheral blood mononuclear cells from a patient with a CD4+CD8+T-prolymphocytic leukemia (T-PLL) and from a patient with a CD4-CD8+ T-chronic lymphocytic leukemia (T-CLL), in the absence of detectable additional mitogenic stimuli. Proliferation of leukemic T cells is induced by both whole Igs and Fab' fragments of anti-HLA class I MoAbs, arguing in favor of their direct interactions with the proliferating cells as the mechanism underlying the mitogenic effect. This interpretation is also supported by the ability of anti-HLA class I MoAbs to induce proliferation of leukemic T-cell preparations, depleted of accessory cells. DNA synthesis in T-CLL and T-PLL cells is preceded by expression of G1-specific messenger RNAs, ie. c-myc, 2F1, Tac, and interferon-gamma, in activated cells. Cell proliferation is inhibited by the protein kinase C inhibitor H7, indicating that activation of this enzyme is required for the mitogenic effect of anti-HLA class I MoAbs. The latter inhibit the proliferation of T-CLL cells as well as that of normal T cells stimulated with anti-CD3 MoAbs and enhance that of both types of cells stimulated with anti-CD2 MoAbs. In addition, anti-HLA class I MoAb Q6/64 in combination with anti-CD2 MoAb 9.6 or MoAb 9-1 induces proliferation of leukemic T cells to a greater extent than the individual MoAbs, but is not mitogenic for normal T cells. Anti-HLA class I MoAbs restore the cytolytic activity of T-CLL cells that is lost after 5 days of incubation of control medium, suggesting that HLA class I antigens may mediate a signal contributing to the activation state. The present results indicate that leukemic T-cell proliferation can be triggered via HLA class I molecules and suggest a potential role for these antigens in the in vivo growth of malignant clones.

Antibodies, Monoclonal↗

PubMed1991

Effect of recombinant fibroblast interferon and recombinant immune interferon on growth and the antigenic phenotype of multidrug-resistant human glioblastoma multiforme cells.

To study the effect of drug resistance on the response of stage IV astrocytomas to interferon, a human glioblastoma multiforme cell line, GBM-18, was transfected with an expression-vector plasmid containing a human multidrug resistance (MDR) gene (pHaMDR1/A), and clones surviving in colchicine were isolated. GBM-18 multidrug-resistant subclones displayed cross-resistance to other chemotherapeutic agents, including vincristine, doxorubicin, and dactinomycin. The multidrug-resistant phenotype was reversible when GBM-18 multidrug-resistant cells were cultured in colchicine and the calcium-channel blocker verapamil. The level of the MDR1 gene (also known as PGY1) message was increased in GBM-18 multidrug-resistant cells selected for increased resistance to colchicine, and this effect was not correlated with an amplification of the MDR1 gene. In both parental GBM-18 and GBM-18 multidrug-resistant cells, growth was suppressed to a greater degree when cultures were treated with the combination of fibroblast interferon (IFN-beta) and immune interferon (IFN-gamma). Parental cells and multidrug-resistant subclones varied in their de novo and/or interferon-modulated expression of HLA class I and class II antigens, a high-molecular-weight melanoma-associated antigen, and intercellular adhesion molecule 1 (ICAM-1). Of the antigens tested, ICAM-1 and HLA class I antigens were the most sensitive to enhanced expression induced by IFN-beta and IFN-gamma when used alone or in combination. The results of the present study indicate that multidrug-resistant human glioblastoma multiforme cells retain their increased sensitivity to the antiproliferative activity of the combination of IFN-beta plus IFN-gamma, and differences in antigenic phenotype are apparent in independent multidrug-resistant glioblastoma multiforme clones.

Antibodies, Monoclonal↗

PubMed1991

Human high-molecular-weight melanoma-associated antigen mimicry by mouse antiidiotypic monoclonal antibody TK7-371.

Since the human high-molecular-weight melanoma-associated antigen (HMW-MAA) represents a useful target to implement active specific immunotherapy with mouse antiidiotypic monoclonal antibody (mAb), the present study is aimed at developing and characterizing mouse antiidiotypic mAbs which bear the mirror image of the determinant defined by the anti-HMW-MAA mAb TP61.5. To this end, a BALB/c mouse was immunized with the syngeneic mAb TP61.5. Screening of the 703 generated hybridomas showed that 13 of them secrete antiidiotypic mAbs which inhibit the binding of the immunizing mAb TP61.5 to melanoma cells by at least 75%. The dose of antiidiotypic mAb required to inhibit by 50% the binding of mAb TP61.5 to melanoma cells ranged between 4 and 200 ng. The 13 antiidiotypic mAbs recognize conformational idiotypes, since they did not react in Western blotting with the heavy and light chain of mAb TP61.5 isolated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Furthermore, the 13 antiidiotypic mAbs did not react with 23 mAbs which recognize 13 determinants of the HMW-MAA distinct from that defined by mAb TP61.5. Analysis of the 13 antiidiotypic mAbs for their ability to elicit cellular and humoral anti-HMW-MAA immunity showed that only mAb TK7-371 elicited a delayed-type hypersensitivity reaction to HMW-MAA-bearing cells in syngeneic hosts and anti-HMW-MAA antibodies in BALB/c mice and in rabbits. Since rabbits express the HMW-MAA, the present results indicate that the antiidiotypic mAb TK7-371 can induce humoral immunity to self HMW-MAA. Therefore, the antiidiotypic mAb TK7-371 may be an efficacious immunogen to implement active specific immunotherapy in patients with melanoma.

Animals↗

PubMed1991

Diversity in the fine specificity and idiotypic profile of mouse anti-HLA-DR monoclonal antibody elicited with the syngeneic anti-idiotypic monoclonal antibody F5-830.

Four hundred and sixty-six hybridomas were generated from a BALB/c mouse immunized with the syngeneic anti-idiotypic mAb F5-830 that recognizes an idiotope in the Ag-combining site of mAb AC1.59. At an appropriate concentration, the latter reacts with a determinant expressed by HLA-DR1, DRw8, and DRw9 Ag and subtypes of HLA-DR4 and DRw6 allospecificities. Serologic and immunochemical assays identified eight anti-HLA-DR anti-anti-idiotypic mAb. They are heterogeneous in their reactivity with a panel of HLA-typed B lymphoid cells: like mAb AC1.59, the anti-anti-idiotypic mAb MA1/38, MA1/40, MA1/47, and MA1/98 recognize the determinant shared by HLA-DR1, DRw8, and DRw9 Ag and subtypes of HLA-DR4 Ag. On the other hand, the anti-anti-idiotypic mAb MA1/52, MA1/157, MA1/281, and MA1/285 have a more restricted reactivity, inasmuch as the corresponding determinant(s) is detectable on only some of the allospecificities recognized by mAb AC1.59. Each anti-anti-idiotypic mAb varies in its extent of reactivity with HLA-DR allospecificities. These results suggest differences in the fine specificity of anti-HLA-DR anti-anti-idiotypic mAb and in the structural characteristics of the mAb AC1.59 defined determinant shared by HLA-DR1, DRw8, and DRw9 Ag and subtypes of DR4 allospecificities. Furthermore, the anti-anti-idiotypic mAb are heterogeneous in terms of expression of idiotopes and of their spatial relationship with their Ag-combining site. The heterogeneity in the characteristics of anti-HLA-DR antibodies elicited with anti-idiotypic mAb F5-830 suggests that the Id cascade triggered by immunization with incompatible HLA allospecificities may account for the changes in the anti-HLA antibody specificity that have been observed in the course of an immune response to mismatched HLA alloantigens.

Animals↗

PubMed1991

Human high molecular weight melanoma-associated antigen mimicry by mouse antiidiotypic monoclonal antibody MK2-23. Characterization of the immunogenicity in syngeneic hosts.

Previous studies have shown that the mouse antiidiotypic mAb MK2-23 elicited with the syngeneic anti-human high molecular weight melanoma-associated Ag (HMW-MAA) mAb 763.74 elicits anti-HMW-MAA antibodies in syngeneic hosts and in patients with melanoma. The present investigation has characterized the fine specificity of antibodies elicited by mAb MK2-23, tested its ability to induce delayed-type hypersensitivity reaction to HMW-MAA-bearing melanoma cells and analyzed the variables that influence the immunogenicity of mAb MK2-23. The anti-HMW-MAA antibodies elicited by mAb MK2-23 recognize the same population of molecules recognized by mAb 763.74, react with the same (or spatially close) determinant(s) and express the idiotopes recognized by mAb MK2-23 in their Ag-combining sites. The antiidiotypic antibodies that bind to HMW-MAA have a lower titer than those that do not. These results in conjunction with those obtained in mice using a suboptimal immunization schedule suggest that the idiotope(s) that mimic(s) the mAb 763.74-defined determinant of the HMW-MAA is less immunogenic than those that do not. mAb MK2-23 induces a delayed-type hypersensitivity reaction to HMW-MAA-bearing melanoma cells. Therefore, mAb MK2-23 represents the first example of mouse antiidiotypic mAb that induces a cellular and humoral immunity to a human tumor-associated Ag (TAA), because the previously described mouse antiidiotypic mAb that bear the mirror image of TAA have been shown to induce only humoral anti-TAA immunity. The immunogenicity of mAb MK2-23 is markedly enhanced by its conjugation to keyhole limpet hemocyanin and its administration with FA. Furthermore, the number of immunizations and the doses of mAb MK2-23 injected influence its immunogenicity, although to a lower extent than conjugation to a carrier and mixing with an adjuvant. The information derived from the present investigation represents a useful background to optimize the immunization schedule with mAb MK2-23 in patients with melanoma.

Animals↗

PubMed1991

Cloning and in vitro expression of a melanoma-associated antigen immunogenic in patients with melanoma.

The purpose of this study was to identify human melanoma-associated Ag (MAA) that are immunogenic in patients, because these molecules may be useful immunogens to implement active specific immunotherapy. To this end, an expression cDNA library constructed from the human melanoma cell line A375 was screened with sera from patients with melanoma. A 1029-bp cDNA (designated D-1) was isolated. Its nucleotide sequence showed no significant homology with viral and mammalian sequences stored in GE-NETYX. cDNA D-1 hybridized to a 2.0-kb mRNA species from human melanoma, neuroblastoma, erythroleukemia, B lymphoid, and T lymphoid cell lines but not from a renal carcinoma cell line, PBL, and cultured skin fibroblasts. The D-1 clone produced a fusion protein that displayed a significantly higher reactivity with sera from patients with melanoma than from healthy controls. Furthermore, D-1 fusion protein induced in mice antibodies that immunoprecipitated a 50-kDa component from cultured human melanoma cells. The structural properties of D-1 MAA are different from those of previously described MAA. These results suggest that the approach we have applied may be useful to identify novel MAA expressed by melanoma cells. Furthermore, the immunogenicity of recombinant D-1 protein suggests that it may be a valuable immunogen to implement active specific immunotherapy in patients with melanoma, if additional experiments show that it has the appropriate tissue distribution.

Amino Acid Sequence↗

PubMed1991

Differential expression of melanoma associated antigens in acral lentiginous melanoma and in nodular melanoma lesions.

The reactivity in an avidin-biotin complex immunoperoxidase reaction with a large panel of anti-human melanoma associated antigen (MAA) and anti-HLA monoclonal antibodies of 24 primary and 11 metastatic acral lentiginous melanoma (ALM) lesions was compared to that of 12 primary and 12 metastatic nodular melanoma (NM) lesions. The expression of the membrane bound vitronectin receptor, Mr 110,000 MAA, Mr 97,000 MAA, and intercellular adhesion molecule-1 was significantly lower in both primary and metastatic ALM lesions than in their NM counterparts. Furthermore, primary ALM lesions displayed a significantly lower expression than primary NM lesions of the membrane bound high molecular weight melanoma associated antigen (HMW-MAA), Mr 110,000 MAA, Mr 100,000 MAA, 9-O-acetyl-GD3, GD2-GD3, and GD2, of the cytoplasmic monoclonal antibody 465.12 defined MAA and of transferrin receptor and of HLA-DQ and DP antigens; ALM metastases expressed a significantly lower level of carcinoembryonic antigen-MAA than NM metastases. These antigenic differences do not reflect an antigenic paucity of ALM cells, since ALM lesions express a higher level of T4-tyrosinase than NM lesions and a level of HLA Class I antigens similar to that of NM lesions. In view of the use of HMW-MAA, Mr 97,000 MAA, and GD3 in immunoscintigraphy and/or in immunotherapy, it is noteworthy that the three antigens are expressed in a similar high percentage of ALM metastases and of primary and metastatic NM lesions, while the HMW-MAA is expressed in a markedly lower percentage of primary ALM lesions than Mr 97,000 MAA and GD3. However, the degree of heterogeneity of HMW-MAA within a positive primary ALM lesion, as measured by the percentage of stained melanoma cells, is lower than that of Mr 97,000 MAA and GD3. The expression of the antigens investigated in ALM and NM lesions was not correlated with the presence of lymphocyte infiltrates, melanin content of melanoma cells, and epithelioid and spindle type of melanoma cells in the lesions. On the other hand, the survival of patients with ALM was inversely correlated with the expression of intercellular adhesion molecule 1 or HMW-MAA in their primary lesions. A potential role of HMW-MAA in the course of the disease is suggested by its significantly higher expression in metastatic than in primary ALM lesions.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1991

Expression of intercellular adhesion molecule-1 (CD54) on hematopoietic progenitors.

The distribution of intercellular adhesion molecule-1 (ICAM-1), a ligand for lymphocyte function antigen-1, on hematopoietic tissue was determined using the anti-ICAM-1 monoclonal antibody CL203.4 with flow cytometry and short-term semi-solid hematopoietic progenitor cultures. After timed incubation in media with fetal bovine serum, 29% of erythroid burst-forming units (BFU-E), 24% of erythroid colony-forming units (CFU-E), and 52% of granulocyte-macrophage colony-forming units (CFU-GM) bone marrow progenitors expressed ICAM-1. This finding, which is consistent with the detection of ICAM-1 on acute non-lymphoblastic leukemic blasts, is at variance with recent reports. ICAM-1 was also detected on bone marrow blasts, proerythroblasts, promyelocytes, and cells of monocyte/macrophage lineage, but was not detected on erythroblasts, normoblasts, neutrophilic myelocytes, metamyelocytes, bands, or on most lymphocytes. These results indicate that maturation of cells of the erythroid and myeloid lineage is associated with loss of ICAM-1. The distribution of ICAM-1 on bone marrow progenitors, early precursor cells, and accessory cells in conjunction with the function of this molecule in cell-cell interactions suggests that ICAM-1 may play a role in the cell-cell and cell-stromal interactions that regulate hematopoiesis.

Antibodies, Monoclonal↗

PubMed1991

HLA class II molecules on monocytes regulate T cell proliferation through physical interaction in the CD3 activation pathway.

HLA class II molecules are involved in the OKT3-induced T cell activation, since monoclonal antibodies (mAb) to monomorphic determinants of class II antigens are able to inhibit T cell proliferation. This effect involves several of the events leading to T cell activation and proliferation, i.e. interleukin (IL) 1, IL 6 and IL2 secretion and IL2 receptor expression. The main target of the inhibition is represented by monocytes, and the interference of anti-class II mAb in the direct interaction of monocytes with T cells is likely to play a relevant role in the inhibition mechanism. To test this hypothesis, we investigated in the present study the effect of anti-class II mAb on the proliferation of T cells stimulated with mAb OKT3 in the presence of paraformaldehyde-treated monocytes. We show that the inhibition of proliferation is specific and dose dependent, and seems to involve particular class II epitopes. Addition of fixed monocytes to inhibited T cell cultures restores proliferation to a moderate extent, only if monocytes are added within the first 12 h of culture, suggesting that class II antigens or spatially related molecules deliver signals concurrently with the mitogenic stimulus. The blocking capability of anti-class II mAb was not restricted to the CD4+ or the CD8+ T cell subsets, suggesting that, under inhibitory conditions, these mAb affect other structures on the T cell surface, relevant to the monocyte-T cell interaction.

Antibodies, Monoclonal↗

PubMed1991

Molecular abnormalities in the expression of HLA class-I antigens by melanoma cells.

Testing of a panel of cultured human melanoma cells with radiolabelled anti-HLA-class-I monoclonal antibodies (MAbs) in a binding assay has shown lack of reactivity of FO-I and SK-MEL-33 cells and low reactivity of SK-MEK-19 cells. SDS-PAGE analysis of the components immunoprecipitated from the 3 intrinsically radiolabelled melanoma cell lines by antibodies to the 2 subunits of HLA-class-I antigens has not detected beta 2-mu in the immunoprecipitates from melanoma cells FO-I and SK-MEL-33 and only a low level of HLA-class-I heavy chain in the immunoprecipitate from SK-MEL-19 cells. Northern blotting analysis with probes specific for HLA-class-I heavy chain and for beta 2-mu indicates that the abnormalities in HLA-class-I-antigen expression reflects a defect at the transcriptional level in FO-I cells and at the post-transcriptional level in SK-MEL-19 and in SK-MEL-33 cells. FO-I, SK-MEL-19 and SK-MEL-33 cells represent useful models to analyze the molecular mechanisms underlying the loss of HLA-class-I-antigen expression which is often associated with malignant transformation of melanocytes and to characterize the role of HLA-class-I antigens in the biology of melanoma cells and in their interactions with effector cells.

Antibodies↗

PubMed1991

T-cell receptors and ICAM-1 expression in renal allografts during rejection.

Sixty-two biopsies taken from 38 kidney grafts were studied for 15 histological and 10 immunohistological parameters. The biopsies were divided into three groups, according to the clinical diagnosis at the time they were performed: group 1, rejection (n = 43); group 2, other causes of dysfunction (n = 10); and group 3, stable function (n = 9). Histological signs of acute rejection included diffuse interstitial infiltrate, tubular basement membrane damage, mononuclear leukocyte infiltration, and congestion of the peritubular capillaries. Immunoperoxidase staining with monoclonal antibodies to ten markers showed a statistically significant association between detection of T-cell receptor subunits alpha-beta (TcR2) and gamma-delta (TcR1) on infiltrating lymphocytes and of intercellular adhesion molecule-1 (ICAM-1) in tubular cells and acute rejection. These results suggest that T-cell receptors and ICAM-1 may be useful markers to differentiate acute rejection from renal graft dysfunctions due to other abnormalities.

Adult↗

PubMed1991

Histiocytosis X arising in Hodgkin's disease: immunophenotypic characterization with a panel of monoclonal antibodies.

This report describes the antigenic profile of the proliferating cells of pulmonary histiocytosis X (HX) in a patient treated with chemotherapy for Hodgkin's lymphoma; the association of pulmonary HX and Hodgkin's disease has rarely been described in the literature. The histopathological diagnosis of HX was confirmed with the aid of monoclonal antibodies (mAbs) to CD4, CD1a, and polyclonal serum anti S-100 protein. The phenotype of HX cells has been analysed using a panel of mAbs against HLA class I A, B, C monomorphic determinants, locus A and B, beta 2-microglobulin, HLA class II distinct monomorphic determinants, DP, DQ, DR, intercellular adhesion molecule-1 (ICAM-1) and vitronectin receptors. Our results indicate that HX cells express HLA class I and II, including locus A, locus B and DP, DQ, DR, like their normal counterpart (represented by Langerhans cells) and detectable levels of ICAM-1 but not vitronectin receptors. We would like to stress the possibility of the association of HX and Hodgkin's lymphoma extending the immunophenotypic profile of HX cells.

Adult↗

PubMed1991

Potentiation of growth suppression and modulation of the antigenic phenotype in human melanoma cells by the combination of recombinant human fibroblast and immune interferons.

Administration of interferon as a single therapeutic regimen in cancer patients with various neoplasias has had only limited efficacy in ameliorating the negative clinical course of their disease. In the present study, we have evaluated the effect of recombinant human fibroblast (IFN beta) and immune (IFN gamma) interferon, alone and in combination, on growth, differentiation and the expression of class I and II histocompatibility locus antigens (HLA) and melanoma-associated antigens on the human melanoma cell line H0-1. The effect of combinations of interferons on the antigenic profile of human melanoma cells displaying different organ colonization and spontaneous metastatic potential in athymic nude mice was also determined. H0-1 cells were more sensitive to the antiproliferative activity of IFN beta than to IFN gamma and the combination of interferons resulted in a potentiation of growth suppression. The antiproliferative effect of both interferons was greater in later-passage than in earlier-passage H0-1 cells, possibly reflecting alterations in the evolving tumor cell population as a result of long-term in vitro propagation and/or the selective outgrowth of cells with an increased growth rate. The enhanced growth suppression observed in H0-1 cells treated with the combination of IFN beta plus IFN gamma was not associated with a significant increase in the level of melanin, a marker of melanoma differentiation, above that observed with either interferon used alone. IFN beta and IFN gamma differentially modulated the expression of class I and II HLA and melanoma-associated antigens in H0-1 cells and a series of melanoma cells with different organ colonization and metastatic potential, including MeWo, MeM 50-10, MeM 50-17, 3S5 and 70W. No consistent potentiation or antagonism in the expression of any specific antigen was observed in any of the melanoma cell lines exposed to the combination of interferons. The present study demonstrates that the combination of IFN beta plus IFN gamma can potentiate growth suppression in H0-1 human melanoma cells and that this effect is not associated with an increase in differentiation or a potentiation in antigenic modulation. In addition, no direct correlation between the expression of any specific antigen or its modulation by IFN beta or IFN gamma, alone or in combination, and organ colonization and metastatic potential in nude mice was observed in the different melanoma cell lines.

Animals↗

PubMed1991

Regression of human melanoma xenografts in nude mice injected with methotrexate linked to monoclonal antibody 225.28 to human high molecular weight-melanoma associated antigen.

Intravenous injections into nude mice of 5 mg/kg methotrexate (MTX) linked to the antibody to human high molecular weight-melanoma associated antigen (HMW-MAA), monoclonal antibody (mAb) 225.28, an IgG2a, on days 1, 4, 7, 10 and 14, starting 24 h after subcutaneous inoculation of 2 x 10(6) cultured human M21 melanoma cells inhibited mean tumor volume by 90% on day 14 and by 65% on day 50 after the beginning of the treatment. Injections of equimolar amounts of free MTX and MTX linked to normal mouse IgG or to an isotype-matched myeloma protein did not inhibit tumor growth significantly. MTX linked to mAb 225.28 did not inhibit the xenograft of a subline of human melanoma cell line M21 without detectable expression of HMW-MAA. In a clonogenic assay, the MTX-225.28 conjugate was three times more potent in inhibiting the growth of M21 melanoma cells than free MTX, but did not inhibit the growth of kidney carcinoma cells Caki-1, which do not express high-Mr MAA. In contrast, MTX linked to the mAb DAL K29, reacting with kidney carcinoma cells Caki-1, inhibited their growth but did not affect that of melanoma cells. M21 melanoma cells isolated from the residual tumor of a mouse treated with the MTX-225.28 conjugate did not differ in their reactivity with mAb 225.28 and in their sensitivity to MTX when compared with M21 cells from an untreated mouse.

Animals↗