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W Harel

Publications and source records attributed to W Harel.

18 recordsLinked to original sources
PubMed2001

Optimization of intracerebral tumour protection by active-specific immunization against murine melanoma B16/G3.12.

Development of brain metastases despite extracerebral response to systemic immunotherapy is a common problem in melanoma patients. We have previously described a murine melanoma vaccine of interferon-gamma (IFNgamma)-treated, irradiated syngeneic B16/G3.12 and allogeneic (Cloudman) melanoma cells, plus the adjuvant DETOX, that is protective against subcutaneous (93%) or intracerebral (69%) syngeneic challenge. This study aimed to optimize this vaccine. Groups of nine or 10 mice were immunized five times in 5 weeks with: (i) complete vaccine +/- IFNgamma (VAC+, VAC-); (ii) syngeneic 2 x 106 G3.12 cells plus DETOX (Syn+D), (iii) 2 x 106 allogeneic Cloudman cells plus DETOX (Allo+D); (iv) VAC+ without DETOX (no DETOX); (v) DETOX alone (DETOX); or (vi) phosphate buffered saline (PBS). Mice were challenged subcutaneously with 104 viable G3.12 (or Cloudman cells) and after 35 days intracerebrally with 104 G3.12 cells. Expression of H-2 antigens (measured using fluorescence-activated cell sorting), splenocyte cytotoxicity (measured using 51Cr release) and median overall survival (OAS) were analysed using the log-rank test. VAC+, VAC- and G3.12 mice were equally protected from subcutaneous (s.c.) and intracerebral (i.c.) melanoma challenge (OAS 65 days for s.c., 30 days for i.c.). Protection was less (P < 0.05) in DETOX mice (48 days for s.c.), PBS mice (47 days for s.c., 21 days for i.c.) or no DETOX mice (51 days for s.c.). Allo+D mice showed s.c. (59 days) but not i.c. protection (20 days). IFNgamma incubation did not increase the effect in either the challenge cells or the vaccine cells (P > 0.05). Specific cytotoxicity was seen with G3.12 targets in VAC+ (27%) but not PBS (2%; P < 0.05) mice with equal NK (YAC-1) lysis (10% versus 7%; P< 0.05). Optimal protection against s.c./i.c. experimental murine melanoma was yielded by irradiated syngeneic cells plus DETOX. DETOX alone was not active. Upregulation of H-2 antigens with IFNgamma under these conditions does not augment protection.

Animals↗
PubMed1998

IVIG adverse reactions: potential role of cytokines and vasoactive substances.

BACKGROUND AND OBJECTIVES: A clinical study was conducted to determine the effect of IVIG infusion rates on adverse experiences (AE) and on serum levels of cytokines and vasoactive substances. MATERIALS AND METHODS: Forty-two healthy volunteers were randomized into 3 groups with maximum IVIG infusion rates of 0.04, 0.06, and 0.08 ml/kg/min, and a final dose of 0.5 g IgG/kg body weight. RESULTS: Adverse reactions were noted only at the highest infusion rate of 0.08 ml/kg/min, except in 1 subject infused at 0.06 ml/kg/min. There were significant increases in IL-6 (p = 0.011) and thromboxane B2 (p = 0.007) in AE subjects as compared to non-AE subjects. CONCLUSION: IVIG-induced adverse reactions occur more often with rapid infusion rates and may be mediated by elevated levels of inflammatory cytokines and vasoactive substances.

Adult↗
PubMed1994

Increased effectiveness of interferon alfa-2b following active specific immunotherapy for melanoma.

PURPOSE: To determine whether interferon alfa-2b (IFN-alfa; intron-A, Schering Corp, Kenilworth, NJ) can induce a remission in patients previously treated with active specific immunotherapy (therapeutic melanoma vaccine) without response. PATIENTS AND METHODS: Eighteen patients with disseminated melanoma who had failed to respond to at least five injections of Melacine therapeutic melanoma vaccine (Ribi ImmunoChem Research, Inc, Hamilton, MT) were then treated IFN-alfa after a 4-week interval. IFN-alfa 5 or 6 x 10(6) U/m2 was self-administered three times a week subcutaneously by melanoma patients for at least 2 months. Computed tomographic (CT) scans of the chest, abdomen, and pelvis and magnetic resonance imaging of the brain were performed within 4 weeks before treatment as a baseline, and then at 2-month intervals during treatment to evaluate response. All 18 patients were HLA-typed before treatment. The frequency of cytolytic T-cell precursors (pCTL) in the blood had been measured weekly in 13 of the patients during treatment with Melacine. RESULTS: Eight of 18 patients (44.4%) had a major objective clinical response induced by IFN-alfa, including site-specific complete remissions in five. Responses lasted a median of 11 months. The median survival duration of the responders has not been reached, and exceeds 32 months. The group as a whole had a median survival duration of 10.1 months, and nonresponders lived 7.3 months. Cytolytic T-cell precursors had been increased by immunization in all five responding patients tested, but also in five of eight nonresponders. There was no association of response to IFN-alfa with specific HLA phenotypes, in contrast to our previous results with melanoma theraccine alone. CONCLUSION: These data suggest an additive effect of active specific immunotherapy and IFN-alfa on the objective response rate, perhaps through upregulation of HLA molecules and tumor-associated antigens on the tumor cell by IFN-alfa, after immunization of the patient by Melacine. This treatment may have improved survival over that expected in metastatic melanoma.

Adult↗
PubMed1993

Active specific immunotherapy of melanoma with allogeneic cell lysates. Rationale, results, and possible mechanisms of action.

Since 1985, we have conducted clinical trials with a therapeutic melanoma vaccine (melanoma theraccine). Mechanical lysates of two melanoma cell lines chosen for their complementary characteristics were combined with the adjuvant DETOX and injected subcutaneously on weeks 1, 2, 3, 4, and 6 for one or two courses and then monthly in patients with objective clinical responses. Of 106 patients, 20 had objective clinical regression of tumor masses, 5 with complete responses. The median duration of response was 21 months. Twelve patients lived at least 2 years, with a median survival of nearly 3 years. Two of them are free of disease for > 2 and > 6 years, respectively. However, it was not necessary to achieve complete remissions to cause an increase in survival, and most of the long-surviving patients have one or more (stable) residual nodules. The pace of the disease process was clearly slowed in those individuals. A rise in the level of cytotoxic T-lymphocyte precursors in the blood (pTC) correlated with clinical response. Only those patients who had a rise in pTC had a remission. In addition to "classical" CD8+ Tc, CD4+ Tc were cloned from the blood of immunized patients. Melanoma-specific Tc of both types that killed autologous melanoma but not matched lymphoblastoid cells were detected. Allogeneic melanoma cell lines were also killed, with mainly HLA-A2/28 and HLA-B12/44/45 degenerate restriction. CD4+ Tc were restricted by HLA Class I antigens, as judged by their killing of HLA Class II-negative melanomas and blocking by anti-class I antibodies. Other CD4+ clones were blocked by both anti-HLA Class I or anti-Class II MHC monoclonal antibodies, and only two were blocked only by anti-HLA Class II. Immunohistory revealed CD4+ and CD8+ T cells in lesions under rejection, but the predominant cells were macrophages, suggesting delayed-type hypersensitivity as a possible mechanism. Clinical responses were found most often in patients with HLA-A2/28, -B12/44/45, and -C3, particularly when two or more of those alleles were present. This may have been due either to (1) similarity of MHC antigens between one of the immunizing melanomas and the patient's melanoma or (2) the intrinsic importance of these MHC molecules in presenting melanoma-associated antigens to Tc in vivo. IFN-alpha 2 b salvaged 8 of 18 patients who failed with the theraccine, regardless of MHC phenotype, perhaps through upregulation of MHC and tumor epitopes on the autochthonous tumor.

Antibodies, Neoplasm↗
PubMed1993

Protection against experimental cerebral metastases of murine melanoma B16 by active immunization.

Melanoma patients often develop brain metastases despite effective systemic immunotherapy against melanoma. We have attempted to establish a mouse model to develop strategies to combat this problem. Immunization of C57BL/6 (H-2b) mice with a combination of the syngeneic G3.12/BM2 melanoma (a B16 subclone) and the allogeneic Cloudman-S91 melanoma was effective in preventing the growth of 10,000 viable, s.c. injected G3.12 cells in 93% of the mice. Irradiated whole tumor cells pretreated with gamma-interferon for 2 days were most effective. A nonspecific adjuvant (DETOX) was injected routinely together with the tumor cells. Active immunization with 2 different doses of irradiated melanoma cells (1 x 10(5) or 2.5 x 10(6) cells/injection x 5 injections) protected against intracerebral challenge with 200 live G3.12 cells in 69% of the mice. This challenge caused the death of all control mice within 30 days. T-cell-mediated, tumor-specific cytotoxicity against G3.12 melanoma was demonstrated in the spleen of immunized mice. Histological observations in the brain, 80 days after tumor challenge, indicated complete eradication of the melanoma, but although CD4+ and CD8+ T-cells and macrophages were present, their number was low. Gliosis was present in both immunized and control animals. Thus, in this murine melanoma model syngeneic mice were protected from death by s.c. and intracerebrally inoculated tumor cells if pretreated with a sufficient number of irradiated syngeneic and allogeneic melanoma cells and an immunological adjuvant. Whether this regimen can treat established tumors of the brain, alone or in combination, is uncertain. Yet its success suggests that the "blood-brain barrier" impeding immunity to tumors may not be absolute.

Animals↗
PubMed1993

Clonal analysis of in vivo activated CD8+ cytotoxic T lymphocytes from a melanoma patient responsive to active specific immunotherapy.

To study in vivo activated cytolytic T cells, CD8+ T cells clones were isolated from a melanoma patient (HLA A2, A11) treated with active specific immunotherapy for 5 years. CD8+ T lymphocytes, purified by fluorescence-activated cell sorting, were cloned directly from the peripheral blood without antigen-presenting cells in the presence of irradiated autologous melanoma cells and recombinant interleukin-2 (IL-2) and IL-4. These conditions were inhibitory to de novo in vitro immunization. Of the 28 cytolytic CD8+ T cell clones, 21 lysed the autologous melanoma cell line (M7) but not the autologous lymphoblastoid cell line (LCL-7) nor the two melanoma cell line, M1 (HLA A28) and M2 (HLA A28, A31), used to immunize the patient. The remaining 7 clones were also melanoma-specific, although their reactivities were broader, lysing several melanoma cell lines but not HLA-matched lymphoblastoid cells. Eight clones from the first group, ostensibly self-MHC-restricted, were expanded for further analysis. All expressed cluster determinants characteristic of mature, activated T cells, but not those of thymocytes, naive T cells, B cells or natural killer (NK) cells. They also expressed CD13, a myeloid marker. Of the 8 clones, 3 expressed both CD4 and CD8, but dual expression was not correlated with specificity of lysis. Two CD8+ and 2 CD4+ CD8+ clones were specific for the autologous melanoma cells, the other 4 were also reactive against other HLA-A2-positive melanomas. Cytotoxicity for both singly and doubly positive clones was restricted by HLA class I but not class II antigens. Analysis of the RNA expression of the T cell receptor (TCR) V alpha and V beta gene segments revealed heterogeneous usage by the A2-restricted clones and, perhaps, also by the broadly melanoma-specific clones. Apparent TCR-restricted usage was noted for the self-MHC-restricted clones; 2 of the 4 expressed the V alpha 17/V beta 7 dimer. Since the T cell clones were derived from separate precursors of circulating cytotoxic T lymphocytes (CTL), the V alpha 17/V beta 7 TCR was well represented in the peripheral blood lymphocytes of this patient. In summary, we show that melanoma cells presented their own antigens to stimulate the proliferation of melanoma-reactive CD8+ CTL. CTL with a range of melanoma specificities and different TCR alpha beta dimers were encountered in this patient, perhaps as a result of hyperimmunization.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Detection of melanoma-reactive CD4+ HLA-class I-restricted cytotoxic T cell clones with long-term assay and pretreatment of targets with interferon-gamma.

Twenty-five CD4+ cytotoxic T lymphocyte (CTL) clones were obtained from the peripheral blood or tumor tissues of melanoma patients undergoing active specific immunotherapy. Melanoma-reactive T cells were cloned by limiting dilution using either autologous or allogeneic melanoma cells to stimulate their proliferation. Sixteen of the clones reacted against autologous melanoma cells but not against the autologous lymphoblastoid cell line, which we defined as "melanoma-specific." Optimal demonstration of the lytic activity of CD4+ CTL required a 16-h incubation period and an effector:target cell ratio of 40:1. In addition, a 24-h pre-incubation of the target melanoma cells with 100 U interferon (IFN) gamma consistently augmented lysis by these CD4+ CTL, increasing it from a mean level of 20% to one of 52%. Lysis by 8 of the 11 melanoma-reactive CD4+ T cell clones was exclusively HLA-class-I-restricted, as judged by blocking with monoclonal antibodies (mAb). Five of these HLA class-I-restricted clones were reactive only with the autologous melanoma cells, while the other 3 clones were also reactive with allogeneic melanoma cells. In all cases, the T cells and melanoma targets shared at least one HLA class I allele, usually HLA-A2, HLA-C3 or HLA-B62. Interestingly, lysis by 2 of the 11 clones was inhibited by both anti-HLA-class-I or -HLA-class-II mAb, while lysis by 1 other clone was inhibited by neither. HLA class I molecules and several accessory molecules were maximally expressed by the melanoma target cells, both in terms of distribution and copy number before IFN gamma treatment. Thus, IFN gamma may have acted by increasing the expression of melanoma-associated epitopes as presented by HLA class I (or HLA class II) molecules. A proportion of human CD4+ CTL appeared to recognize melanoma-associated epitopes presented by the HLA class I molecule, although their lytic potency may be less than that of their CD8+ counterparts.

CD4-Positive T-Lymphocytes↗
PubMed1992

Association of HLA phenotype with response to active specific immunotherapy of melanoma.

PURPOSE: Only a proportion of patients with disseminated melanoma who were immunized successfully with a therapeutic melanoma vaccine (theraccine) had a major clinical response. We investigated whether there was a correlation between their HLA phenotypes and the likelihood of a clinical response. PATIENTS AND METHODS: Seventy patients with disseminated melanoma who were treated with melanoma theraccine were HLA-typed serologically. The two melanoma cell lines used in the theraccine also were typed by serology and cDNA probes (for class II). Results were analyzed to see whether any alleles were present or absent in responders consistently. RESULTS: The HLA class I alleles A2 (and the cross-reacting A28), B12 (and its split B44 and B45), and C3 were found to be associated with clinical remission. The effects of these alleles on response were apparent when two or more of the alleles were analyzed together. There was a 38% response rate in those 24 patients with two or three of the alleles compared with 20% in the group as a whole. CONCLUSIONS: These data support two distinct possibilities between which we cannot yet distinguish. Responses may be more likely when there is a close match between the HLA molecules in the theraccine and the patients' own molecules. Alternatively, certain types of HLA class I molecules present in the patients may facilitate rejection of autochthonous melanomas by efficiently presenting melanoma-associated antigens to cytotoxic T cells.

Adult↗
PubMed1991

Lymphocytes cytotoxic to uveal and skin melanoma cells from peripheral blood of ocular melanoma patients.

To study antitumor immunity in patients with choroidal melanoma, T cells were generated from the peripheral blood of choroidal melanoma patients by mixed lymphocyte/tumor cell culture (MLTC). Because autologous tumors are generally unavailable, an allogeneic choroidal melanoma cell line, OCM-1, was used as the specific stimulus. Lymphocyte cultures from 27 patients were characterized by cell-surface phenotypes, patterns of reactivity towards cells of the melanocytic origin and T-cell-receptor gene usage. Antimelanoma reactivity was found in cell-sorter-purified CD4+ and CD8+ T cell subsets. To analyze this reactivity, sorter-purified CD4+ and CD8+ cells from a MLTC were cloned by limiting dilution in the presence of exogenous interleukin-2 and interleukin-4 as well as irradiated OCM-1. Under these conditions, CD4+ T cells did not proliferate, perhaps because of the absence of antigen-presenting cells. However, CD8+ grew vigorously and 29 cytolytic CD8+ T cell clones were isolated. On the basis of their pattern of lysis of OCM-1, a skin melanoma cell line M-7 and its autologous lymphoblastoid cell line LCL-7, the clones were categorized into three groups. Group 1, representing 52% of the clones, lysed all three target cells, and are alloreactive. However, since OCM-1 and M-7 did not share class I antigens, these clones recognized cross-reactive epitope(s) of the histocompatibility locus antigen (HLA) molecule. Group 2, constituting 28% of the clones, lysed both the ocular and skin melanoma cell lines but not LCL-7, and were apparently melanoma-specific. Unlike classical HLA-restricted cytolytic T lymphocytes, these T cells might mediate the lysis of melanoma cells via other ligands or a more degenerate type of HLA restriction. For the latter, the HLA-A2 and -A28 alleles would have to act interchangeably as the restriction element for shared melanoma-associated antigen(s). Group 3, representing only 10% of the T cell clones, was cytotoxic only to OCM-1, but not to M-7 or LCL-7. These clones may recognize antigens unique to ocular melanoma cells. Our data suggest that choroidal melanoma patients can recognize melanoma-associated antigens common to both ocular and cutaneous melanoma cells, and presumbly their autologous tumor. Thus, choroidal melanoma, like its skin counterpart, may be responsive to immunotherapeutic regimens such as active specific or adoptive cellular immunotherapy.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1990

Increased lysis of melanoma by in vivo-elicited human lymphokine-activated killer cells after addition of antiganglioside antibodies in vitro.

Thirty-nine melanoma patients were treated with cyclophosphamide (350 mg/m2) followed 3 days later by 5 daily doses of interleukin 2 (3.6 million units/m2 i.v.) weekly for 2 weeks. This cycle was repeated at least twice with a 1-week interval between cycles. Natural killer and lymphokine-activated killer (LAK) cell activity in peripheral blood mononuclear cells were measured before treatment and on the last day of each cycle by chromium release assays. Development of LAK activity of greater than 10 lytic units was correlated with a clinical response. There was no correlation between natural killer activity and clinical response. Antibody-dependent cell-mediated cytotoxicity of in vivo-induced LAK cells after the addition of mouse monoclonal antibodies (MAbs) in vitro was measured in 30 cases on the last day of each interleukin 2 cycle. Anti-GD3 MAbs MB3.6, 11C64, 6H4, and R24 increased LAK cell cytotoxicity against GD3-positive GD2 melanoma cells while anti-GD2 MAb 14.18 increased LAK cell cytotoxicity against GD3-negative GD2-positive melanoma cells. MAb 9.2.27 (IgG2a) directed against a chondroitin sulfate proteoglycan and its core protein with a molecular weight of 250,000 (p250) on human melanoma cells did not mediate antibody-dependent cell-mediated cytotoxicity. The effector cells in these antibody-dependent cell-mediated cytotoxicity. The effector cells in these antibody-dependent cell-mediated cytotoxicity reactions were Leu-19 positive. In preincubation experiments the MAbs showed superior binding to the melanoma target cells than to effector cells. Our results show that low dose interleukin 2 preceded by low dose cyclophosphamide effectively induces LAK cells in vivo. The cytotoxicity of these in vivo-activated LAK cells can be augmented in vitro by mouse MAbs against glycolipid antigens on the tumor.

Antibodies, Monoclonal↗
PubMed1990

Active-specific immunotherapy for melanoma.

Twenty-five patients with metastatic melanoma were treated with a therapeutic vaccine ("theraccine") consisting of allogeneic melanoma lysates and a novel adjuvant, DETOX (Ribi ImmunoChem Research, Inc, Hamilton, MT). Each patient received 200 antigenic units (20 x 10(6) tumor cell equivalents) subcutaneously on weeks 1, 2, 3, 4, and 6. Clinical responses included one complete remission, three partial remissions, and a long-term (17-month) stability. Two other patients had mixed responses, with partial remissions of numerous subcutaneous nodules. Sites of responsive disease included primarily the skin, but ileal, breast, and a liver metastasis also responded. Removal of residual lesions in patients with partial remissions, whose other lesions had disappeared during treatment, led to long disease-free survivals. The median duration of remission was 17 months, with four of the five responders alive for at least 24 months after treatment. An increase in precursors of cytolytic T cells (CTLs) correlated with clinical outcome, when complete, partial, and mixed responses and long-term stability were considered. The CTLs recognized melanoma-associated antigens on many cell lines, but not other types of tumor or normal lymphocytes. Skin-test reactivity to melanoma antigens and serum antibodies against the melanoma cells was unrelated to clinical response. Toxicity was minimal, restricted largely to minor soreness at the site of injection. Only five patients, four of whom were treated with repeated courses, developed severe granulomas. These results confirm that active-specific immunization with allogeneic lysates of melanoma administered with the adjuvant DETOX can induce immunity to melanoma, and can induce regressions of disease in a proportion of patients with metastatic disease with little toxicity.

Adjuvants, Immunologic↗
PubMed1989

Low-dose cyclophosphamide and low-dose interleukin-2 for malignant melanoma.

We have studied the effects of low-dose recombinant interleukin-2 preceded by low-dose cyclophosphamide on malignant melanoma. Thirty eight outpatients aged from 25 to 75 years were treated with interleukin-2, 3.6 million Cetus units/m2 i.v. daily for five days on two successive weeks beginning three days after 350 mg/m2 of intravenous cyclophosphamide. This schedule was repeated at least twice more with a one-week interval between cycles, usually at the same dosage level. Ten of the 38 patients (26.3%) had clinically significant remissions: two complete (5.3%), seven partial (18.4%), and one ongoing, long-term (greater than 18 mo) "minor" response (2.6%). Four others (10.5%) had shorter minor responses and four (10.5%) a mixed response. One patient with disease restricted to the skin had a complete remission, while the other patient with a complete remission had had three lung nodules and an enlarged hilar lymph node. It was gratifying that one of the major sites of disease responding to treatment was the liver. Two complete and two partial remissions (i.e., greater than 50% regressions for greater than four weeks at this site) were obtained in 10 patients with liver involvement. Lung metastases also responded in four of 16 patients (one complete and three partial remissions). Subcutaneous nodules responded in seven of 21 patients (two complete, five partial remissions), while lymph node metastases diminished significantly in four of 14 patients (one complete, three partial remissions). The median duration of response was nine months (range, 1.5-20 months), with four patients treated for more than one year. Toxicity was moderate and controllable, and only two patients required hospitalization, both overnight. Lymphokine activated killer cell activation was induced in 24 of 38 patients, including all nine of the major responders. Conversely, none of 14 patients without lymphokine activated killer cell activation had a significant clinical remission. This regimen appeared to be as effective in melanoma as those involving ex vivo activation of lymphokine activated killer cells, and was more tolerable than therapy with high doses of interleukin-2.

Adult↗
PubMed1988

Active specific immunotherapy for melanoma: phase I trial of allogeneic lysates and a novel adjuvant.

A Phase I trial of active specific immunotherapy for melanoma was performed to measure the toxicity and immunological effects of the therapy. A mixture of mechanical lysates (homogenates) of two melanoma cell lines was injected together with a novel adjuvant, DETOX, into 22 patients. Several types of cell-mediated and humoral immunity to melanoma-associated antigens were measured serially. In the 17 patients with measurable disease, the sizes of lesions were also noted serially. At least six patients per group were injected s.c. with either 100, 200, or 400 antigenic units (approximately 10, 20, and 40 million tumor cell-equivalents) of the lysates mixed with 0.25 ml of DETOX s.c. on weeks 1, 2, 3, 4, and 6. Three patients at each dose level also received 300 mg/m2 of cyclophosphamide i.v. 4 days before the start of immunization. Evidence for successful immunization was obtained in 13 of the 22 patients. An increase in the frequency of peripheral blood cytolytic lymphocyte precursors reacting against melanoma cells occurred in 12 patients, as measured by a limiting dilution assay involving in vitro re-exposure to irradiated melanoma cells for 9-10 days. Eight of the 12 patients had received cyclophosphamide. By cold-target competition assays, these cytolytic lymphocytes appeared to be atypical T-cells, which recognized melanoma-associated antigens on several allogeneic lines without apparent major histocompatibility complex restriction. An increase in antibody titers against melanoma-associated antigens, measured by enzyme immunoassay, was found in five of 22 patients, and a change in delayed hypersensitivity against the melanoma lysate, in three patients. Responses were found at all three dosage levels of lysate, without an obvious dose optimum. No toxicity except minor local soreness was noted. Therefore, no maximum tolerable dose was defined. Five of 17 patients with measurable lesions had a remission of their melanoma, two complete and three partial, with three additional minor responses. A patient whose complete remission lasted 5.5 months, has no evidence of disease 22+ months after entry onto the study, with the aid of surgical resection of small s.c. recurrences on two separate occasions. Sites of regression included s.c. nodules, lymph nodes, and pulmonary nodules, with no responses in liver, adrenal gland, or bone. The patients who had an increase in cytolytic lymphocyte precursors comprised all eight with a clinical remission (five major, three minor). In contrast, none of the seven patients lacking an increase in cytotoxic lymphocytes had a clinical response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1988

Effectiveness and tolerability of low-dose cyclophosphamide and low-dose intravenous interleukin-2 in disseminated melanoma [corrected].

We studied the effects on melanoma of low-dose recombinant interleukin-2 (IL-2) preceded by low-dose cyclophosphamide (CYC). Twenty-seven outpatients, aged 25 to 75 years, were treated with IL-2, 3.6 million U/m2 intravenously (IV), daily for five days on 2 successive weeks beginning three days after 350 mg/m2 of IV CYC. This schedule was repeated at least twice more at 1-week intervals. Six of 24 patients (25%) who received more than one 2-week cycle of treatment had a remission, one complete and five partial, with minor responses in eight others (33.3%). Three patients with rapidly progressive disease, who received only one cycle, were excluded from the analysis of response. The responses comprised remissions of liver metastases in two patients, one of them complete, two complete and two partial regressions of subcutaneous metastases, partial remission of lymph node metastases, and a partial remission of lung nodules. The mean duration of response exceeded 5 months, with two patients treated for greater than 1 year. Toxicity was moderate and controllable and only two patients required hospitalization, both overnight. Lymphokine-activated killer (LAK) cell activation was induced in 17 of the 24 patients, including all six responders, while none of seven patients without LAK activation had a remission. This regimen appeared to be as effective in melanoma as those involving ex vivo activation of LAK cells, and was generally tolerable to patients in all age groups.

Adult↗
PubMed1985

An enzyme immunoassay for the detection of antisperm antibodies.

A simple and reliable enzyme-linked immunosorbent assay (ELISA) for the detection of antisperm antibodies has been developed in our laboratory. The antigen for the solid phase was produced by sperm sonication while antihuman globulin conjugated to alkaline phosphatase was used as the developing reagent. The conditions and reagents of the assay were chosen to give a mild treatment of the antigen, simple manipulation during washing steps, and nontoxic and readily available reagents. The results were compared to a conventional microscopical method routinely used in our laboratory that detects agglutinating antibodies to human spermatozoa. In 96% of all cases antibodies detected by the microscopical method were also detected by ELISA. Moreover there were some cases where no antisperm antibodies could be demonstrated by microscopy, but gave a positive reaction with ELISA. These were usually cases of unexplained oligospermia, agglutinates in the ejaculate, and bad motility or low viability of the sperms. These results, and also titration experiments of positive samples demonstrate the higher sensitivity of the ELISA by comparison with microscopical methods.

Agglutination Tests↗