PubMed Health⌕ Search

Biomedical subjects

A Balsari

Publications and source records attributed to A Balsari.

At least 73 records · Page 4Linked to original sources
PubMed1992

Inhibition of the biological activity of human interferon-gamma by antipeptide antibodies.

To study the domain(s) responsible for the different biological activities of human interferon-gamma (HuIFN-gamma), rabbits were immunized with peptides corresponding to the five most hydrophilic amino acid sequences of the lymphokine. The resulting antisera were able to recognize both the immunizing peptide and the native protein. Antibodies to the carboxy-terminal region (amino acids 125-137) of HuIFN-gamma were able to interfere with the immunomodulating, antiviral, and antiproliferative activities of the lymphokine. Inhibition of the antiproliferative and antiviral activity was also observed using antibodies raised against the amino-terminal region (amino acids 4-16) and amino acids 80-95, respectively, but to a lesser extent than that observed with antibodies to the carboxyl terminus. The capability of these antibody preparations to partially interfere with only one of the lymphokine's biological activities might be explained by a mechanism of steric hindrance. The use of polyclonal antibodies allowed us to limit the presence of epitopes responsible for recombinant (r)HuIFN-gamma biological activities to the carboxy-terminal region.

Antibodies↗
PubMed1991

Anti-drug monoclonal antibodies antagonize toxic effect more than anti-tumor activity of doxorubicin.

Monoclonal antibodies (MAbs) able to bind epitope(s) of drug molecule can interfere with the biologic action of the drug. This is known and already exploited in some instances of practical relevance, as in the reversal of the digoxin effect. Similar antidotal action is exhibited by MAbs reacting with a cytotoxic antibiotic, doxorubicin (DXR), and in such a way as to induce differential neutralization of drug action. Indeed, within certain limits, the cytotoxic action of DXR in vitro as well as in vivo is more effectively neutralized on normal than on tumor cells, with consequent increase in therapeutic index.

Animals↗
PubMed1991

Purification of natural human IFN-gamma antibodies.

Natural antibodies to interferon gamma (IFN-gamma) were found in patients suffering from various viral infections, but also at weak titers in healthy individuals. In the present study we describe a one-step chromatographic procedure for the purification of the anti-IFN-gamma antibodies from human Ig preparations, using a recombinant IFN-gamma-coupled Sepharose CL4B affinity column. The antibodies to IFN-gamma were eluted from the column using 3 different methods without loss of immunological activity. They were found to be Ig, mostly of the IgG1 subclass, and, in the biological assay, to be able to neutralize the de novo expression of Fc receptor sites induced by IFN-gamma on U937 cells.

Autoantibodies↗
PubMed1991

Antigen-specific immunodepression induced by doxorubicin-BSA conjugate in mice.

Injection into mice of the anthracycline cytotoxic derivative Doxorubicin (DXR) covalently bound to bovine serum albumin (BSA) was associated with antigen-specific depression of the primary (but not of the secondary) antibody reaction to the carrier, whereas DXR and BSA injected in the form of a mixture caused no such effect. Tetanus toxoid completely prevented the carrier-specific inhibiting effect when administered at the same time as, but not three days before or after, injection of the DXR-BSA conjugate. Possible mechanisms of the antigen-specific immunodepression and its prevention by unrelated antigen are discussed.

Animals↗
PubMed1990

Protection of mice against tumor growth by immunization with an oncogene-encoded growth factor.

The K-fgf/hst oncogene encodes a growth factor of the fibroblast growth factor (FGF) family that is secreted and transforms cells through a mechanism of autocrine cell proliferation. K-fgf-transformed cells are highly tumorigenic in immunocompetent allogeneic and syngeneic animals. BALB/c mice were immunized with a bacterial fusion protein consisting of a portion of the MS2 polymerase and of the human K-FGF precursor lacking only the first 4 amino acids or with a recombinant protein corresponding to the mature, secreted form of K-FGF (176 amino acids). They were then challenged with syngeneic K-fgf- or H-ras-transformed cells. Vaccinated animals exhibited a significant degree of protection against tumor induction, which was specific for K-fgf-transformed cells and correlated with the ability of the immunized mice to produce high titers of anti-K-FGF antibodies. Thus immunization with a single oncogene product can protect animals against tumor cells expressing this oncogene.

Animals↗
PubMed1989

Skin and perivascular toxicity induced experimentally by doxorubicin.

Extravasation of antitumor drugs and particularly doxorubicin (DXR) can be followed by skin ulceration and slowly evolving perivascular necrosis. DXR lesions have some characteristics in common with those induced by ionizing radiation and, with respect to gross morphology, are reminiscent of skin lesions induced by necrotizing agents. Time course and histopathology of toxic phenomena induced by intradermal or perivascular injection of various doses of either DXR or caustic chemicals have been studied in hairy outbred and hairless inbred (MF1 hr/hr) mice. The latter strain has been found to be intrinsically more sensitive to DXR induced toxic effects, particularly as far as perivascular administration is concerned. Long lasting lesions and, in a few cases, systemic involvement have been observed. On the contrary, necrotic foci induced by caustic chemicals rapidly regressed in both strains. The perivascular administration model, which has not been previously investigated, appears to be representative of what happens in clinical conditions and can be of use for assessing either skin toxicity of antitumor compound or the protective effect of candidate antidotes.

Animals↗
PubMed1988

Monoclonal antibodies against doxorubicin.

Hybridomas which secrete monoclonal antibodies (MAbs) reacting with doxorubicin (DXR), a widely used anthracycline cytotoxic antibiotic, have been obtained by fusing NSO/P3 mouse myeloma cells with spleen cells from BALB/c mice immunized with DXR-BSA conjugate. The best producer among the several clones obtained was expanded and the secreted MAb (MAD2) purified and characterized. MAD2 cross-reacts to varying degrees with anthracycline compounds such as some DXR analogues and derivatives, but does not recognize anthracene and anthraquinone structures, with the exception of weakly reacting Mitoxantrone. MAD2 and the panel of MAbs which are at present being purified may become a tool for studying the relevance of different domains of the anthracyclin molecule in terms of biologic activity.

Animals↗
PubMed1988

Tumorigenicity and dissemination of primary and metastatic human melanomas implanted into different sites in athymic nude mice.

In the present study, the growth features and metastatic capacity of human primary and metastatic melanomas transplanted by different routes in nude mice was examined. Eight different human melanoma early cell cultures derived from 3 primary tumors, 1 local recurrence and 4 metastatic lesions of 6 melanoma patients were characterized for cell surface HLA (class I and II) and melanoma-associated antigens and karyotype. These tumors were then transplanted in CD-1 outbred nude mice by subcutaneous, intraperitoneal and intrasplenic routes. It was found that 7 out of 8 melanomas were tumorigenic after subcutaneous implantation without giving rise to metastases; 5 out of 7 melanomas grew when injected intraperitoneally and 3 of them disseminated to peritoneal organs and infiltrated intraperitoneal lymph nodes, liver and pancreas; of 8 melanomas implanted intrasplenically 4 grew in the spleen or invaded intraperitoneal lymph nodes, liver, pancreas, ovaries or lungs. Primary and metastatic melanomas did not differ in the pattern of dissemination. In fact, 2 out of 4 metastases and 1 of 3 primary tumors and 1 recurrence disseminated after intrasplenic or intraperitoneal inoculation. Heterogeneity in the growth pattern of different metastases of the same melanoma patient was also found. No correlation could be detected between the metastatic ability of melanoma cells studied and clinical stage of patients, tumor cell karyotype abnormalities, modal number or with the antigenic phenotype.

Animals↗
PubMed1986

Control of human melanoma growth in nude mice by autologous allo-activated peripheral blood lymphocytes.

Human peripheral blood lymphocytes (PBL) were activated in vitro by means of a pool of allogeneic PBL from normal donors and then evaluated for in vivo activity against human melanoma cells xenografted in splenectomized and irradiated athymic (nude) mice. The subcutaneous (s.c.) growth of human melanoma cells was inhibited by intravenous (i.v.) injection, 2 hr later, of such allo-activated, autologous and allogeneic PBL in 7/8 and in 6/9 mice respectively. Unstimulated PBL were ineffective. When allo-activated patients' lymphocytes were administered 3 days after s.c. implantation of autologous melanoma cells, inhibition of tumor growth was observed in 1/6 mice. A significant delay in tumor appearance was noted in the remaining animals. Unstimulated as well as allo-activated, lymphokine-releasing helper-enriched human PBL had no effect on melanoma xenografts, indicating that the tumor inhibition by tumor-cytotoxic allo-activated PBL was not due to recruitment of murine immuno-competent cells by human lymphokines. These results indicate that allo-stimulated, tumor-cytotoxic human PBL given i.v. to nude mice can circulate and inhibit the growth of autologous or allogeneic human melanoma cells implanted s.c.

Animals↗
PubMed1986

Systemic administration of autologous, alloactivated helper-enriched lymphocytes to patients with metastatic melanoma of the lung. A phase I study.

A phase I study was carried out to test the feasibility and toxicity of infusing large numbers of autologous, alloactivated helper lymphocytes into patients with metastatic melanoma. Patient peripheral blood lymphocytes (Pt-PBL) obtained by lymphopheresis and expressing the helper phenotype BT5/9 were separated and stimulated for 48 or 72 h with a pool of PBL from four to six healthy donors. Patients were then infused with such activated lymphocytes over a 2-3 h period. A total of 4 phereses and infusions (2/week for 2 weeks) were carried out for each cycle in each patient. Of the five patients treated, two received a second round of infusions. Infusion of autologous PBL stimulated in vitro for 48 h caused chills, fever, headache, and increased blood pressure. All symptoms disappeared in 2-3 h and were easily controlled by appropriate therapy. When lymphocytes were given after 72 h of allostimulation, no or very mild toxicity was observed. Serum chemistry, coagulation, autoimmunity, and urine analysis showed no gross abnormalities during therapy or follow-up of the patients. Immunological parameters (OKT4/OKT8 ratio, NK activity and cytotoxic T cell activity to autologous melanoma) were evaluated before starting the therapy, during its course and during the 3 to 6 months follow-up. The OKT4/OKT8 ratio increased significantly but transiently soon after the first course of infusions in one of the two patients tested. NK activity increased after 75-100 days in the three patients tested and in one of them it was high even after 180 days. No correlation between NK activity and prognosis was apparent. Cytotoxicity to autologous tumor was assessed in two patients, only of one of whom exhibited an increased activity from 75 to 180 days, which was associated with a prognosis better than that of the negative patient. Five patients were treated: two had progressive disease, two had stable disease for 5 and 6 months, respectively. In the first of these patients, a new cycle of lymphocyte infusions was carried out which caused a measurable reduction of lung tumor nodules whose growth, however, resumed 4 months later. This patient died 14 months after the onset of therapy. The fifth patient had a partial regression of pulmonary and intracranial metastases after therapy, but eventually died 3 months later. These results indicate that infusion of a high numbers of autologous, allostimulated helper PBL is a feasible and safe procedure, which could therefore be used in future studies of adoptive immunotherapy of cancer.

Antibodies, Monoclonal↗
PubMed1985

Autologous cellular immune response to primary and metastatic human melanomas and its regulation by DR antigens expressed on tumor cells.

Evidence for heterogeneity of several biological features of human malignant melanoma (Me) like morphology, cytogenetics, oncogenes activation, antigenic expression, metastatizing capacity and procoagulant activity are briefly reviewed in an attempt to distinguish findings related to primary vs. metastatic lesions. In our own studies monoclonal antibodies were used to study expression of MHC class I, class II products and of Me-associated antigens (MAA) on primary and metastatic Me cells. High expression of class I antigens was found in a high percentage of both primary and metastatic tumors, whereas DR and MAA showed a significant variation (from 3 to 90% of cells) in expression both in primary and in metastatic Me. When autologous cell-mediated immune responses were evaluated, it was found that Me cells from primary tumors but not those from lymph node metastases were able to stimulate autologous lymphocytes to proliferate and become cytotoxic for autologous Me. Clonal analysis of cytotoxic lymphocytes was then carried out in order to see whether the lack of lymphocytes reactivity to metastatic cells was due to the absence or to a low frequency of cytotoxic cells in the unstimulated PBL. CTL clones cytotoxic for autologous Me (Auto-Me) cells were indeed isolated. Three classes of CTL clones were identified: 1) one which is cytotoxic for Auto-Me; 2) a second one which lyse Auto-Me and allogeneic Me; and 3) a third one which is cytotoxic for Auto-Me and allogeneic normal and neoplastic cells. Metastatic Me cells, however, had the ability to suppress the stimulation of autologous PBL by alloantigens or IL-2. This effect was dose-dependent and was not due to absorption of IL-2 by Me cells. Since it has been reported that Me cells express class II MHC antigens, we investigated whether there was any correlation between autologous immune responses and DR expression on Me cells. Autologous lymphocytes stimulation was found to occur only with DR+ Me cells from primary lesions, whereas metastatic cells, either DR+ or DR-, did not stimulate autologous PBL. Moreover, the suppressive effect of metastatic Me cells was associated with their expression of DR antigens. The modulation of DR antigens on Me cells by Interferon-gamma correlated positively with their suppressive capacity. Thus, it appears that primary Me can behave differently from the metastatic one in their interactions with the immune system of autologous host. These findings suggest that DR antigens on Me cells may have an important role in the regulation of autologous immune responses.

Antigens, Neoplasm↗
PubMed1985

Allostimulation of patients' lymphocytes generates both T and NK-like cells cytotoxic for autologous melanoma.

Killing of autologous melanoma (auto-Me) was obtained with pooled allostimulated peripheral blood lymphocytes (PBL) in 34/42 cases and found not to be due to a cross-reactivity between melanoma and allogeneic normal antigens. To see whether generation of tumour cytotoxic PBL by allostimulation was due to release of IL-2, PBL from 34 patients were divided into two aliquots and stimulated either by alloantigens or IL-2. Allostimulated PBL were cytotoxic for auto-Me in 30/34 cases (85%) whereas IL-2 generated tumour cytotoxic cells in 22/34 cases (64%). Lysis of K562, a target for monitoring NK-like activity, was obtained in 95-100% of cases with both stimuli. A similar frequency of OKT3+, OKT4+, OKT8+ and HNK1+ cells was found in PBL activated by allostimulation and IL-2, whereas a higher frequency of OKM1+ cells was evident in IL-2-stimulated PBL. Cold-target competition studies indicated that allostimulation generated at least two different types of effectors, one lytic to auto-Me but not to K562, and the other which lysed both targets. Allostimulated, FACS-separated T3- cells killed both auto-Me and K562 cells whereas T3+ cells lysed only auto-Me. It is concluded that allostimulation generated two subpopulations of auto-Me killer cells, one of the T lineage and the other NK-like, which both can destroy auto-Me targets.

Antibodies, Monoclonal↗