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S Ferrone

Publications and source records attributed to S Ferrone.

At least 91 records · Page 5Linked to original sources
PubMed1995

Modulation of adhesion molecule CD54 expression on CD34+ hematopoietic progenitors.

Multiple cellular adhesion molecules are constitutively expressed on hematopoietic progenitors. CD54 (ICAM-1), a member of the immunoglobulin supergene family, has recently been shown to be present on a subset of hematopoietic progenitors. To demonstrate that this adhesion molecule is expressed on the surface of the hematopoietic progenitor following induction rather than in its basal state, we studied the expression of cell surface CD54 on flow-cytometric (FACS) gated progenitors (CD34+; lymph plus blast light scatter). A mean +/- standard deviation (SD) of 2.75 +/- 2.10% was seen for FACS-gated progenitors from freshly isolated bone marrow mononuclear cells (BMMNC) stained with anti-CD54 MAb. Following incubation at 37 degrees C for 20 to 22 hours in media supplemented with heat-inactivated bovine fetal serum (FBS), the percentage of FACS-gated progenitors staining with anti-CD54 MAb increased to 46.28 +/- 18.38. This increase was temperature and time dependent. The percentage of FACS-gated progenitors stained with anti-CD54 MAb did not increase following 20 to 22 hours of incubation at 4 degrees C. Furthermore, a subpopulation of FACS-gated progenitors staining with anti-CD54 MAb was detectable by 5 hours of incubation at 37 degrees C; the percentage of these progenitors staining with anti-CD54 MAb plateaued after 10 hours of timed incubation. Once induced, progenitor cell surface CD54 antigen density remained stable, as evidenced by a constant mean fluorescence intensity of anti-CD54 MAb staining. Three-color immunofluorescent studies showed that induction of CD54 occurred on CD45+ FACS-gated progenitors and that CD54 was induced on a subset of BMMNC expressing CD34 and CD11a, a counter receptor for CD54 that is limited in distribution to leukocytes. CD54 expression was induced to the same degree on FACS-gated progenitors positive or negative for CD19, CD36, and HLA-DR, respectively. These data indicate that CD54 is a unique adhesion molecule as its expression can be induced on CD34+ hematopoietic progenitors, and this induction does not appear to be related to hematopoietic progenitor lineage commitment or maturity.

Antigens, CD↗
PubMed1995

Human high molecular weight-melanoma associated antigen mimicry by mouse anti-idiotypic monoclonal antibody MK2-23: modulation of the immunogenicity in patients with malignant melanoma.

The mouse anti-idiotypic (anti-id) mAb MK2-23 bears the mirror image of the antigenic determinant defined by antihuman high molecular weight-melanoma associated antigen (HMW-MAA) mAb 763.74. The purpose of this study was to evaluate the effect of conjugation to a carrier and administration with an adjuvant and cyclophosphamide (CTX) on the immunogenicity of anti-id mAb MK2-23 in patients with malignant melanoma and to analyze the relationship between development of humoral immunity and survival time of patients. Fifty-eight patients were sequentially entered into four immunization protocols which included administration of mAb MK2-23, mAb MK2-23 conjugated to keyhole limpet hemocyanin (KLH) and mixed with Bacillus Calmette-Guérin (BCG), mAb MK2-23 and CTX, and mAb MK2-23 conjugated to KLH and mixed with BCG and CTX. Six patients could not be evaluated since they withdrew from the clinical trial after the first immunization. Sera were tested for the development of anti-anti-id antibodies, including those reacting with HMW-MAA. Testing of sera for development of antimouse Ig antibodies was used to monitor the immune competence of patients. Conjugation to KLH and administration with BCG markedly enhanced the ability of mAb MK2-23 to induce anti-anti-id antibodies, including those reacting with HMW-MAA. In contrast, pretreatment with CTX had no detectable effect on the ability of mAb MK2-23 to elicit a humoral anti-anti-id response. Kaplan-Meier survival analysis showed that the performance status of patients, anti-anti-id antibody level, and development of anti-HMW-MAA antibodies had an effect on survival time. This effect was found when the survival time was calculated both from the day of the first immunization and from 4 weeks after the first immunization to the end of the study. A multivariate analysis by Cox regression showed that the development of anti-HMW-MAA antibodies was the most important variable for predicting survival, and that performance status was the only variable that significantly added to the prediction of survival. These data have to be interpreted with caution because of the retrospective nature of the analysis. Nevertheless, the present study suggests that mAb MK2-23 represents a useful immunogen to implement active, specific immunotherapy in patients with malignant melanoma.

Animals↗
PubMed1994

Growth inhibition of human melanoma cells in nude mice by antisense strategies to the type 1 insulin-like growth factor receptor.

The growth of human melanoma cells FO-1 in nude mice is strongly inhibited or even abrogated when the cells are stably transfected with a plasmid expressing an antisense RNA to the insulin-like growth factor 1 receptor (IGF-1R) RNA, which causes a marked reduction in the number of IGF-1 receptors. When a tumor arises after a long delay in nude mice, it can be shown that the tumor cells have lost the expression plasmid and that the number of IGF-1 receptors has returned to wild-type levels. The antisense effect is even more remarkable, since the growth of FO-1 melanoma cells in monolayers is not affected by the expression of the antisense RNA. Inhibition of tumorigenesis was also evident when FO-1 melanoma cells were treated with antisense oligodeoxynucleotides to the IGF-1R RNA prior to injection into nude mice. These results confirm in human cells that the IGF-1R plays a dominant role in transformation and tumorigenesis and that its effect on tumorigenesis is more profound than its effect on mitogenesis.

Animals↗
PubMed1994

Sustained high levels of circulating chaperoned interleukin-6 after active specific cancer immunotherapy.

In a phase 1 study of recombinant interleukin-6 (rIL-6) in patients with advanced solid tumors (n = 15), we discovered that the endogenous IL-6 levels, in pretreatment plasma or serum samples, were distributed into two groups. One set of patients (designated "type 1"; n = 9) was characterized by low plasma IL-6 levels (48 to 1,700 pg/mL) as measured using enzyme-linked immunosorbent assays (ELISA) for IL-6. In the second set of patients (designated "type 2"; n = 6), IL-6 ELISAs showed high levels of plasma IL-6 (50 to 600 ng/mL). Neither group had detectable B9 hybridoma cell growth factor activity associated with the IL-6 in their pretreatment plasma or serum. Plasma C-reactive protein (CRP) levels were markedly elevated in type II patients suggesting that the circulating IL-6 was biologically active in vivo. In both groups of patients there was a small but significant increase in B9 activity in the plasma within three hours after rIL-6 administration (n = 5). Gel filtration profiles showed that circulating IL-6 in type 1 patients, 15 to 120 minutes after rIL-6 administration was of approximate mass 20 to 40 kD, whereas in type 2 patients, the IL-6 before and after exogenous rIL-6 administration was indistinguishable and was of an approximate mass of 200 kD. IL-6 immunoaffinity purification of the 200 kD complexes showed these to contain multiple isoforms of IL-6 (14 to 31 kD) and the soluble IL-6 receptor (sIL-6R; 50 to 55 kD). A distinguishing clinical history was that all of the type 2 patients had been actively immunized with an anti-idiotypic monoclonal antibody (MoAb) (MK2-23) 3 to 12 months before initiation of this study for advanced melanoma. An analysis of the plasma IL-6 content in other melanoma patients (n = 16) during antiidiotypic MoAb immunization indicated that marked (up to 600 ng/mL) and sustained (several months) elevations of circulating "chaperoned" IL-6 were induced by active immunization regimens.

Antibodies, Monoclonal↗
PubMed1994

Antigenic profile of mucosal melanoma lesions.

Ten primary and 6 metastatic mucosal melanoma lesions were tested, utilizing the immunoperoxidase reaction with a panel of 26 monoclonal antibodies (MAbs). The latter included MAbs recognizing membrane-bound and cytoplasmic-melanoma-associated antigens, adhesion molecules and their receptors, and HLA Class-I and Class-II antigens. The melanoma lesions displayed differential reactivity with the panel of MAbs. Mucosal melanoma lesions differ from other types of melanoma in their antigenic profile, since they are the only type of melanoma to display a higher expression of p97 MAA, CEA-MAA and NGF-R in primary lesions than in metastatic ones. Furthermore, the pattern of HMW-MAA expression in mucosal melanoma lesions is different from that in nodular and uveal melanoma lesions and only partly resembles that observed in acral lentiginous melanoma lesions. Like other types of melanoma, mucosal melanoma lesions display a heterogeneous expression of HLA antigens, a selective loss of reactivity with some of the anti-HLA Class-I MAbs and a higher frequency of abnormalities in HLA Class-I antigen expression in metastatic than in primary lesions. Expression of HMW-MAA, 110-kDa MAA, p97 MAA, CEA-MAA, NGF-R and GD2 ganglioside in primary melanoma lesions was found to be associated with a poor prognosis. Although preliminary in nature, these results suggest that analysis of mucosal melanoma lesions with MAbs, in conjunction with information about the clinical course of the disease, will contribute to determine the biological and clinical significance of the distinct characteristics of the antigenic profile of mucosal melanoma lesions.

Antibodies, Monoclonal↗
PubMed1994

Kinetics of the immune response and regression of metastatic lesions following development of humoral anti-high molecular weight-melanoma associated antigen immunity in three patients with advanced malignant melanoma immunized with mouse antiidiotypic monoclonal antibody MK2-23.

Active specific immunotherapy has been implemented in patients with advanced malignant melanoma, utilizing the mouse antiidiotypic (anti-id) monoclonal antibody (mAb) MK2-23 which bears the internal image of high molecular weight-melanoma associated antigen (HMW-MAA). In a previous study, development of anti-HMW-MAA immunity in patients with advanced malignant melanoma immunized with anti-id mAb MK2-23 was found to be associated with a statistically significant survival prolongation. Since no information is available about the relationship between development of immunity and clinical response in patients immunized with anti-id mAb, the present study has characterized the kinetics of the immune response in three patients with advanced malignant melanoma who experienced regression of metastatic lesions following immunization with the anti-id mAb MK2-23. The three patients developed anti-mouse IgG antibodies, anti-anti-id antibodies and anti-HMW-MAA antibodies. The anti-HMW-MAA antibodies are mainly IgG, suggesting that the immune response elicited by anti-id mAb MK2-23 is T-cell dependent. The development of anti-HMW-MAA immunity preceded the reduction in the size of metastatic lesions. This temporal relationship suggests but does not prove that the anti-HMW-MAA immunity elicited by anti-id mAb MK2-23 has a beneficial effect on the clinical course of the disease in patients with malignant melanoma. This finding in conjunction with minor side effects associated with repeated administrations of mouse anti-id mAb MK2-23 suggest that active specific immunotherapy with anti-id mAb which bear the internal image of melanoma-associated antigen represents a viable therapeutic approach to malignant melanoma.

Aged↗
PubMed1994

Structural profile of idiotype, anti-idiotype and anti-anti-idiotype monoclonal antibodies in the HLA-DQ3 antigenic system.

Interest in the characterization of idiotype cascades in the HLA antigenic system has been stimulated by their potential role in the immune response to mismatched HLA allospecificities and in the survival of kidney allografts. Since no information is available about the structural organization of idiotypic cascades in the HLA system, we have sequenced the variable regions of the heavy (VH) and light (VL) chains of mouse anti-HLA-DQ3 monoclonal antibody (mAb) KS13 elicited by cell membrane-bound antigens, of syngeneic anti-HLA-DQ3 mAb S2B154 elicited by anti-idiotypic (anti-id) mAb K03-34 and of five syngeneic anti-id mAb elicited by mAb KS13. mAb KS13 and S2B154, which have been previously shown to be very similar in their specificity and idiotypic profile, share several structural characteristics. Their VH and VL regions are encoded by the same VH, VK and JH genes, display relatively similar V(D)J rearrangements and differ only through a few amino acid substitutions. Among the five anti-id mAb elicited by mAb KS13, mAb R1-38 and R18-9 utilize multiple genetic elements that are different from those used by anti-id mAb KO3-34, K03-256 and K03-335. These results indicate that diverse V region combinations can confer an anti-id specificity in the antigenic system analyzed. mAb K03-34, K03-256 and K03-335 originate from the same B cell clone, since they use the same V, D and J genes and possess identical V(D)J rearrangements. The latter three anti-id mAb differ only by point mutations, which have dramatic effects on the HLA-DQ3 antigen mimicry properties of the three anti-id mAb. mAb K03-34 is the only one to induce anti-HLA-DQ3 antibodies both in syngeneic and xenogeneic hosts. The antigen mimicry properties of anti-id mAb K03-34 depend upon its three-dimensional conformation, since no significant amino acid sequence homology has been found between its VH and VL regions and alpha 1 and beta 1 domains of HLA-DQ3 antigens.

Amino Acid Sequence↗
PubMed1994

Increased level of serum HLA class I antigens in HIV infection. Correlation with disease progression.

Analysis of (sHLA-I) antigens in a large number of HIV-positive subjects found a significant increase of their level, but did not detect any change in their molecular profile. Monitoring at yearly intervals for four years of the sHLA-I antigen level in 14 HIV-positive subjects with a normal sHLA-I antigen level at study entry showed a significant correlation between progressive increase of sHLA-I antigen level and disease progression. Furthermore, a Kaplan-Meier plot of the frequency of development of AIDS in 34 patients whose cases were followed for 7 years showed that sHLA-I antigen level is a strong predictor of progression to AIDS. Its predictive value is comparable to that of serum beta 2-mu level, greater than that of serum neopterin, and lower than that of CD4+ T-cell percentage. The predictive value of sHLA-I antigen level in combination with serum beta 2-mu level, neopterin level, or CD4+ T-cell percentage is greater than that of each individual variable. These results suggest that measurement of the sHLA-I antigen level may provide useful prognostic information in HIV-positive subjects.

CD4 Lymphocyte Count↗
PubMed1994

Similar ectopic expression of ICAM-1 and HLA class II molecules in hypertrophic scars following thermal injury.

In previous studies we have shown that HLA Class II antigens are expressed by keratinocytes and fibroblasts in hypertrophic scars. Because of the potential role of immunological events in the pathogenesis of hypertrophic scars, in the present study we have tested hypertrophic scars for the expression of intercellular adhesion molecule-1 (ICAM-1), a molecule which plays an important role in immunological phenomena. Immunoperoxidase staining with anti-ICAM-1 MoAb of 10 hypertrophic scar samples detected this molecule on epidermal keratinocytes and on about 30 per cent of fibroblasts at the site of lymphoid infiltration. The expression of ICAM-1 in hypertrophic scars was similar to that of HLA Class II antigens. Since the concomitant expression of ICAM-1 and HLA Class II by keratinocytes is known to enhance their antigen-presenting properties, the present results support the possibility that immunological events play a role in the disruption of the normal processes of wound healing and tissue remodelling which result in hypertrophic scars.

Adult↗
PubMed1994

HLA-B*3501-peptide interactions: role of anchor residues of peptides in their binding to HLA-B*3501 molecules.

Two HLA-B*3501 binding self-peptides, LPFDFTPGY (37F) and LPGPKFLQY (28H), were isolated from HLA-B*3501 molecules expressed by cultured human B lymphoid cells. Both sequences were consistent with previously reported motifs of HLA-B*3501 binding peptides which carry proline at position 2 and tyrosine at position 9 as anchor residues. Direct binding of these peptides to HLA-B*3501 molecules was quantitated by flow cytometry analysis of RMA-S cells. transfected with the HLA-B*3501 gene (RMA-S-B*3501). Both 37F and 28H peptides bound effectively to HLA-B*3501 molecules. Substitution of amino acids at position 2 and/or 9 of HLA-B*3501 binding peptides markedly reduced their binding to HLA-B*3501 molecules. These results indicate that two anchor residues, proline at position 2 and tyrosine at position 9 are critical in binding of peptides to HLA-B*3501 molecules. Insertion of up to four glycine residues at position 8 of the peptide 37F did not affect its binding affinity to HLA*3501 molecules. These results indicate that long peptides can effectively bind to HLA class I molecules provided that anchor residues are conserved.

Amino Acid Sequence↗
PubMed1994

Anti-idiotypes and their application under autoimmune, neoplastic, and infectious conditions.

Idiotypes and anti-idiotypes are becoming widely used in various experimental applications in multiple fields of research. Administration of anti-idiotypes has been attempted in order to manipulate immune reactions affecting autoimmune, neoplastic, and infectious processes. Immunization with anti-idiotypes and idiotypes may change the autoantibody expression in autoimmune diseases. In certain experimental models administration of anti-idiotypes and idiotypes may even propagate the induction of autoimmune-like disorders. Internal image bearing anti-idiotypes may provide an effective tool in the combat of neoplastic and infectious diseases. Such anti-idiotypes may resemble the structure of neoplastic cell antigen or mimic the composition of a contagious viral antigen. This review will deal in detail with the various aspects of idiotype and anti-idiotype immunomanipulation.

AIDS Vaccines↗
PubMed1993

Vitiligo autoantibodies are effective against melanoma.

BACKGROUND: Vitiligo is a dermatologic disease characterized by local, dispersed, or diffuse white patches on the skin. The disease is defined as an autoimmune disorder because autoantibodies against membranal components of melanocytes are found in the patients' sera. The current study examined whether the autoantibodies reacting with the normal melanocytes could be a potent therapy against melanoma cells. METHODS: The three in vitro assays used to determine the antibody reactivities using a mouse melanoma cell line B-16-F10 and M-14 human melanoma cells as targets are as follows: enzyme-linked immunosorbent assay (ELISA), proliferation assay, and morphologic examination in the presence of antibodies purified from sera of patients with vitiligo. In the in vivo studies, experimental melanoma was intravenously induced in C57BL/6J mice, and the mice were treated by daily intraperitoneal injections with purified immunoglobulin G (IgG) fraction derived either from patients with vitiligo or from healthy subjects. RESULTS: The binding of IgG derived from patients with vitiligo was demonstrated by ELISA: Exposure of melanoma cells to the vitiligo autoantibodies was followed by inhibition of their proliferation capacity. In addition, morphologic alterations exemplified by detachment of the cells from their solid support associated with melanin release were observed in the B-16-F10 cells. Less metastatic foci developed in the lungs of the mice treated with the purified IgG fraction from the sera of patients with vitiligo compared with those treated with purified IgG fraction from healthy subjects. CONCLUSIONS: The results of this study point to the presence of anti-melanoma autoantibodies in the sera of patients with localized and diffuse vitiligo. These antibodies have a destructive effect on melanoma cells in vitro and in vivo.

Animals↗
PubMed1993

Clinical relevance of ICAM-1 expression in primary lesions and serum of patients with malignant melanoma.

Immunohistochemical staining with monoclonal antibodies detected ICAM-1 in about 69% of 55 primary melanoma lesions and in about 89% of 28 metastatic lesions. The average number of melanoma cells stained by anti-ICAM-1 monoclonal antibodies was approximately 65% in both primary and metastatic lesions. ICAM-1 expression in primary lesions was significantly associated with their thickness. Furthermore, ICAM-1 expression in primary lesions was associated with a reduction in the disease-free interval and with survival. At variance with the information in the literature, the association with clinical parameters of the disease did not reach the level of statistical significance. This discrepancy is likely to reflect the inclusion in the present study of a small number of primary lesions with a thickness < 1.5 mm. At variance with recently published data, the level of serum ICAM-1 in 75 patients with malignant melanoma was found to be nonsignificantly different from that in 47 age- and sex-matched controls. The level of serum ICAM-1 was significantly increased only in patients with stage III melanoma with lesions and in those with stage IV melanoma. Two novel and clinically relevant findings of the present investigation are (a) the significantly higher serum ICAM-1 level in patients with liver metastases than in those with metastases in other anatomic sites and (b) the progressive increase of ICAM-1 level in serial blood samples from patients with disease progression. The latter findings suggest that monitoring of serum ICAM-1 level may represent a valuable noninvasive indicator system to detect liver metastases and to monitor the clinical course of the disease in patients with malignant melanoma.

Antibodies, Monoclonal↗
PubMed1993

Differential effect of human and mouse beta 2-microglobulin on the induction and the antigenic profile of endogenous HLA-A and -B antigens synthesized by beta 2-microglobulin gene-null FO-1 melanoma cells.

beta 2-Microglobulin (beta 2-mu) gene-null human melanoma FO-1 cells display lower reactivity with anti-HLA class I monoclonal antibodies (mAb) following transfection with a wild-type mouse beta 2-mu gene (referred to as FO-1C cells) than following transfection with a wild-type human beta 2-mu gene (referred to as FO-1H cells). Furthermore, binding assays with a panel of anti-HLA class I mAb detected higher reactivity of FO-1C cells with mAb TP25.99 than with mAb CR1-S63, CR10-215, CR11-115, TP67, and W6/32 but similar reactivity of FO-1H cells with all the mAb tested. While mAb TP25.99 recognizes a determinant expressed on beta 2-mu-free and beta 2-mu-associated HLA class I heavy chains, the remaining mAb recognize determinants expressed only on beta 2-mu-associated HLA class I heavy chains. The differential effects of mouse and human beta 2-mu on the reactivity with anti-HLA class I mAb of FO-1 cells reflect more than one mechanism. Besides abnormalities in the processing of HLA class I heavy chains associated with mouse beta 2-mu, this molecular complex appears to be unstable on the plasma membrane of FO-1 cells. To analyze the interaction of mouse beta 2-mu with HLA-A and -B antigens, the HLA phenotype of FO-1 cells was determined, using a combination of isoelectric focusing analysis of antigens immunoprecipitated from radiolabeled cells with mAb to monomorphic determinants of HLA class I antigens, binding assays with a limited number of mAb recognizing HLA class I allospecificities, and sequence-specific oligonucleotide probe typing. Although association with mouse beta 2-mu does not cause marked differences in the expression of HLA-A25 and -B8 antigens on the cell surface of FO-1 cells, it causes a selective reduction in the expression of determinants recognized by anti-HLA-A mAb F4/72 and VF19-LL67 and by anti-HLA class I mAb W6/32 on HLA-A25 allospecificities. The differential effect of the association with mouse beta 2-mu on the antigenic profile of HLA-A25 and -B8 antigens may reflect the different characteristics of the amino acids at residue 12, which interact with residue 33 of beta 2-mu. The latter residue is the only one to differ between human and mouse beta 2-mu in the stretch of amino acids interacting with the alpha 1 and alpha 2 domains of HLA class I heavy chains.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Susceptibility of human trophoblast to killing by human complement and the role of the complement regulatory proteins.

The susceptibility of trophoblast to cytolysis by human complement was investigated using cells purified to over 90% from first trimester placentae. Two assay systems were employed to measure the killing of trophoblasts, an antibody-dependent complement-mediated cytolysis and the reactive lysis. The antibody obtained from a patient with Addison's disease reacted specifically with syncytiotrophoblasts and induced a dose-dependent killing of the cells not exceeding 50% even in the presence of excess antibody and complement. The percentage of cells killed by the terminal complement complex in the reactive lysis system was somewhat higher, reaching values of 60%. Immunofluorescence analysis revealed the presence of CD46 and CD59 on all syncytiotrophoblasts, whereas CD55 was only detected on approximately 30% of the cells. Inhibition of CD46 and CD59 resulted in increased susceptibility of syncytiotrophoblasts to complement lysis. The protective function of CD55 could not be evaluated because of its reduced expression on isolated trophoblasts. These results suggest that syncytiotrophoblasts may be killed by complement and that membrane regulators to some extent protect these cells from complement damage.

Antigens, CD↗