Characterization of a murine monoclonal antibody against human esophageal squamous cell carcinoma-associated antigen.

A murine monoclonal antibody (MAb) 2G3 of the IgG1 type was raised using the human esophageal squamous cell carcinoma (SCC) cell line TE-2. Immunoblotting with 2G3 indicated that the antigen recognized by 2G3 has a molecular weight of 34 kD. Its activity was evaluated by immunoperoxidase and immunofluorescence on frozen and paraffin sections of various normal tissues, normal and benign tumors as well as various established cell lines. The pattern of reactivity revealed that the antigen recognized by 2G3 was expressed mainly by esophageal SCC. The only exception was represented by malignant breast tumors, where it reacted weakly. Scatchard analysis using 125I-labelled 2G3 showed that TE-2 has approximately 7.5 times more binding sites than the MCF-7 breast cancer cell line. The use of this new MAb is therefore proposed for the histopathological diagnosis of esophageal SCC.

Dysregulated cytokine production by monocytes from chronic lymphocytic leukemia patients.

The serum levels of proinflammatory cytokines (Tumor Necrosis Factor, Interleukin-1, Interleukin-6) in B-cell Chronic Lymphocytic Leukemia (CLL), and secretion of these cytokines by monocytes from CLL patients has been studied in 27 CLL patients and 20 normal subjects under unstimulated and stimulated conditions. It has been observed that monocyte function is impaired and deficient in CLL patients. The cytokine secretion though decreased in unstimulated cultures, was found to reach normal levels as far as IL-6 and TNF are concerned, indicating a possible role of an in vivo suppressive factor. The observed defect in cytokine production may have an important implication for the immune system of the patients.

Abnormal levels of proinflammatory cytokines in serum and monocyte cultures from patients with chronic myeloid leukemia in different stages, and their role in prognosis.

Interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), primarily monocyte-derived cytokines, form a group of proinflammatory cytokines with related and overlapping spectra of activities. The role of these cytokines in chronic myeloid leukemia (CML) has been investigated. A distinctive pattern of cytokine secretion has been found in chronic myeloid leukemia in chronic phase (CML-CP), in blastic crisis (CML-BC) and in normal subjects. Serum IL-6 levels in CML-CP and CML-BC were significantly raised compared with normal controls (p = 0.0026 for CML-CP and p = 0.0011 for CML-BC). IL-6 was significantly elevated in blastic crisis of CML (103.5 +/- 20.77 pg ml-1) compared with CML-CP (37.35 +/- 10.88 pg ml-1; p = 0.014). IL-6 serum levels were found to correlate significantly with peripheral blood monocyte counts and bone marrow blast and basophil counts. We have analysed monocyte/macrophage function with respect to their ability to produce IL-1, IL-6 and TNF-alpha, spontaneously as well as in response to LPS, in comparison with normal controls. A direct correlation of IL-6 levels in unstimulated and stimulated cultures with bone marrow blast and basophil counts has been observed. From these results it is inferred that the monocyte function is impaired in CML patients, and the cytokine secretion is deficient. Our limited data suggest that serum IL-6 levels may play an important role as a prognostic marker for CML.

Serum tumor necrosis factor for monitoring response of hepatic veno-occlusive disease to pentoxiphyllin--a case report.

Hepatic veno-occlusive disease (VOD) is the second most common cause of death after autologous bone marrow transplantation (ABMT). A patient with multiple myeloma undergoing ABMT developed classic features of hepatic VOD. He responded to treatment with pentoxiphyllin. Serum tumor necrosis factor (TNF) levels showed remarkable correlation with the severity of VOD and response to therapy.

Adoptive immunotherapy using lymphokine-activated killer (LAK) cells and interleukin-2 for recurrent malignant primary brain tumors.

Ten patients with recurrent malignant primary brain neoplasms were treated with adoptive immunotherapy using lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2). Nine patients had supratentorial glioma and they received multiple intratumoral instillations of LAK cells through reservoir-catheter system or burrhole. The other patients with disseminated subarachnoid metastases from posterior fossa medulloblastoma received immunotherapy via lumbar subarachnoid route. A partial and transient clinical response was observed in two patients. following the therapy, and a cystic transformation of the essentially solid tumour was noted on the CT scans of these two patients. No significant clinical or radiological response to the treatment was observed in the remaining 8 patients. The results of this preliminary study reveal limitations of the regional intratumoral adoptive immunotherapy using currently available techniques and provide sufficient evidence of its effectiveness to warrant further investigations.

Tumor necrosis factor as marker for monocyte function in chronic myeloid leukemia.

The intactness of monocyte function in chronic myeloid leukemia (CML) patients as assessed by their ability to secret tumor necrosis factor was evaluated. Monocytes from CML patients continued to respond to lipopolysaccharide (LPS) stimulation even during the refractory period, suggesting different pathways for stimulation by LPS and malignant processes.

Characterization of a pan-lymphocyte monoclonal antibody useful in differentiating leukemic from normal myeloid progenitors and monocytes from macrophages.

A monoclonal antibody (McAb) designated 3A2 that recognizes a 51 kDa epitope having surface density of 37 x 10(8) per MOLT-4 cells is described. This epitope appears to be expressed on (i) lymphocytes at all stages of differentiation; (ii) leukemic myeloid progenitors; (iii) peripheral blood monocytes (MO). The epitope is specifically absent from normal myeloid progenitors and macrophages. The McAb may, therefore, be useful in studying myeloid lineage leukemias and, as a marker for monocyte to macrophage (MO + MAC) differentiation.

A specific and rapid receptor assay for squamous-cell carcinoma of human esophagus.

A specific radioreceptor assay, for squamous-cell carcinoma of the human esophagus, using 2G3 monoclonal antibody, has been developed for the first time. In this assay a new mathematical parameter of the Scatchard plot has been introduced for the correct measure of binding capacity (BCcm = x cos alpha). This is the perpendicular distance from the origin to the Scatchard plot line. It is always a positive quantity and is directly proportional to both the x and y intercepts for expressing the binding capacity. The assay is highly sensitive and can be used to differentiate various types of esophageal tumors such as squamous-cell carcinoma, adenocarcinoma, ulcerative growth and also a benign growth. BCcm significantly varies in the case of squamous-cell carcinoma tumors compared to adenocarcinoma and other types of tumor of the human esophagus. The assay can be completed in about 4 h and it may be used as a clinical diagnostic test.

Immuno-phenotype and proliferative response of B-cell chronic lymphocytic leukemia.

This study examines the immunophenotypic profiles in both pretreated and treated CLL patients which could be useful from the prognosis point of view. Patients suffering from B CLL and having IgG markers were relatively more aggressive than cells bearing IgM phenotypes. Male predominance is observed in male/female ratio in this disease. B CLL showed heterogeneity by showing reactivity against various T cell markers such as CD5 (present on mature T cells) and also CD4 (T helper/inducer), CD8 (T suppressor/cytotoxic) and a very high percentage of Ia (HLA-DR). The proliferative response to cells to stimulation with PHA and PWM indicated that there is a primary defect in the capacity of these small lymphocytes to undergo a proliferative response due to an intrinsic defect in the B lymphocytes. This study also reflects a maturation arrest in the later developmental stage of B lymphopoiesis. The three findings which are novel are the difference in prognosis between IgG-IgM and IgG, the changes in T cell subsets and the mitogenic response.

Unique monoclonal antibodies against soluble membrane proteins of human CML myelocytes reactive with human myeloid progenitor cells.

Monoclonal antibodies of IgG1 type immunoglobulin, directed against soluble CML antigen isolated from the reactive CML peripheral myelocytes, were reported. These MAbs were further investigated for their reactivity by 125I-Protein-A binding assays, indirect immunofluorescence tests, cytotoxicity, SDS-PAGE, immunoelectrophoresis, and by immunodiffusion suggesting that they recognized antigens specific mostly to undifferentiated cells. These were tested against various leukemic peripheral blood leukocytes, bone marrow cells, established cell lines of various origin, and with many solid tumor cells and demonstrated specific reactivity with CML myelocytes alone and cell lines of myeloid origin. Indirect immunoperoxidase staining of single cell preparation revealed peroxidase localization in most promyelocytes and in few mature myelocytes from CML PBL/BM cells, thus helping in identifying the exact type (morphology) involved in reacting specifically with these MAbs.

Pattern of subtypes of acute lymphoblastic leukemia in India.

Leukemic cells from 124 acute lymphoblastic leukemia (ALL) and 31 chronic lymphatic leukemia (CLL) were examined for sheep erythrocyte receptor (E), surface immunoglobulin (SIg) and their reactivity with a panel of monoclonal antibodies recognizing specific surface antigens including pan-T, Common ALL and Ia antigens. In acute lymphatic leukemia, 33% of patients reveal T-cell receptor associated with higher age group, mediastinal mass and high WBC count. Common ALL was predominant between 2 and 9-yr age group. Among chronic lymphatic leukemia, 2 patients were found to be T-CLL while 29 revealed presence of SIg. Ia antigen was detected in 44.4% of ALL and 64% fo CLL patients. The pattern of surface marker observed in our series may be related to our life style, socio-economic and environmental factors.

Immunity in esophageal carcinoma.

In carcinoma of the esophagus, response to in vivo sensitization with recall antigens and DNCB was markedly depressed with 13% and 16% positivity respectively. Similarly, the number of T-cells was found to be significantly low (24 +/- 14) as compared to normal control (61 +/- 23). Blastogenesis index with PHA was only 1.75 +/- 1.04 in contrast to normal of 6.79 +/- 2.57. This depression was independent of serum albumin level and body weight. Cell-mediated immunity was further depressed following radiotherapy and did not improve following enteral alimentation for 3 weeks. In untreated patients, there was a significant rise in levels of IgA (298 +/- 184 mg/100 ml) as compared to normal (154 +/- 54 mg/100 ml). Levels of IgA did show a downward trend following enteral hyperalimentation. Circulating immune complexes and serum CEA level were elevated in almost 50% of patients. These data confirm the influence of tumor-related impairment of cell-mediated immunity while nutrition appears to affect IgA levels.

Immune status in untreated cervical cancer patients.

Eighty untreated cervical carcinoma patients were tested for their immune status by evaluating levels of circulating T and B lymphocytes and lymphocyte reactivity to PHA. Significant reduction in T lymphocytes and depressed lymphocyte reactivity to PHA was observed following the progression of the disease. However, B lymphocyte levels remained unaffected. The general impairment observed in cell-mediated immunity was found to be more pronounced in the disseminated disease than in the localized group.