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C M Balch

Publications and source records attributed to C M Balch.

At least 127 records · Page 7Linked to original sources
PubMed1986

Interleukin 2 activation of cytotoxic T-lymphocytes infiltrating into human metastatic melanomas.

Tumor infiltrating lymphocytes (TIL) were isolated from 22 tumors obtained from 15 patients with metastatic melanoma. In 18 of the 22 tumors, a substantial number of lymphocytes was isolated with an average lymphoid cell:tumor cell ratio of 1.26. The TIL were predominantly cytotoxic/suppressor T-lymphocytes with an average of 87% Leu4+, 61% Leu2a+, and 18% Leu3a+ cells. There were less than 2% natural killer cells, B-cells, or macrophages. An average of 3.8% (range, less than 0.1 to 8.6%) of freshly isolated TIL bound to autologous tumor cells. Prior to culture, none of the tumor-binding cells (TBC) was cytotoxic as judged by trypan blue exclusion. The frequency of TBC increased to 11.6% after 2 days of culture, and 10% of these TBC developed cytotoxic activity. When interleukin 2 was added to cultures, the frequency of TBC increased, and the frequency of cytotoxic TBC was 2-fold higher compared to control cultures. After 10 days of culture with interleukin 2, TIL increased in number with a concomitant disappearance of tumor cells, whereas there were severe decreases of lymphocytes and no decrease of tumor cells in control cultures. TIL were cultured for 8 to 10 days with recombinant interleukin 2 and tested for cytotoxicity against autologous and allogenic tumor cells and K562 targets in a 4-h 51Cr release assay. rIL2-cultured TIL from all nine patients tested exhibited the highest levels of lysis against autologous tumor cells. Of the nine TIL samples, five exhibited an apparent specificity for autologous melanoma, while four specimens killed both allogenic and autologous melanoma. The ability of TIL to kill K562 targets appeared to parallel the ability to kill allogenic targets. For comparison, recombinant interleukin 2-cultured peripheral blood mononuclear cells from the same patients were assayed for cytotoxic activity against autologous and allogenic melanomas. Unlike some TIL, none of the peripheral blood mononuclear cells exhibited specificity for autologous tumor cells. In summary, TIL isolated from metastatic melanoma patients were predominantly cytotoxic T-lymphocytes with the ability to recognize and kill autologous tumor cells after in vitro culture; interleukin 2 induced proliferation of TIL and augmented their cytotoxic activity such that they eliminated autologous tumor cells.

Cells, Cultured↗
PubMed1986

Subpopulation analysis of human granular lymphocytes: associations with age, gender and cytotoxic activity.

Levels of human blood granular lymphocyte subpopulations were enumerated in 105 healthy donors ranging in age from 0 to 79 years. Using double-label immunofluorescence, subpopulations of granular lymphocytes were enumerated as follows: Leu7+Leu2+, Leu7+Leu3+, Leu7+11-, Leu7+77+ and Leu7-Leu11+. The proportion of cells with granular lymphocyte morphology was determined by Giemsa staining. Natural killer (NK) cell activity against K-562 cells and lymphokine-activated killer activity against non-cultured melanoma cells were examined in parallel. Levels of total Leu7+ and Leu11+ cells increased with age (p = 0.0001) and were higher in males than females (p = 0.001). The total number of cells with granular lymphocyte morphology had an age-related increase (p = 0.001), but were not significantly higher in males than in females (p = 0.07). There was no selective increase in one granular lymphocyte subpopulation versus another since the Leu7+Leu11- (p = 0.0001), the Leu7+Leu11+ (p = 0.0001), the Leu7+Leu2+ (p = 0.0001) and the Leu7+Leu3+ (p = 0.0004) all had similar age-related increases. The one exception was the Leu7-Leu11+ (p = 0.1) granular lymphocyte subset which was low in the first decade of life but had reached maximum levels in the second decade. NK cell activity against K-562 cells was moderately increased with age (p = 0.06) with males and females exhibiting comparable activity. In contrast. lymphokine-activated killer cytotoxicity of non-cultured melanoma cells was similar in all age groups. NK cell activity was highly correlated with levels of morphologically defined granular lymphocytes (p = 0.005) and moderately with total Leu11+ cells (p = 0.06) but not with other subpopulations of granular lymphocytes.

Adolescent↗
PubMed1985

The influence of surgical margins and prognostic factors predicting the risk of local recurrence in 3445 patients with primary cutaneous melanoma.

Risk factors associated with local recurrences were analyzed from a series of 3445 clinical Stage I melanoma patients. In single-factor analysis, tumor thickness, ulceration, and increasing age were highly significantly predictive of recurrence (p less than 0.00001). After 5 years of follow-up, local recurrence rates were 0.2% for tumors less than 0.76 mm thick, 2.1% for tumors 0.76 to 1.49 mm thick, 6.4% for tumors 1.5 to 3.99 mm thick, and 13.2% for tumors 4.0 mm or greater in thickness. Ulcerated melanomas recurred more often than nonulcerated lesions (11.5% versus 1.9%). When analyzed as a continuous variable, increasing age increased the risk of local failure. In multifactorial analysis, all of these three factors remained independently predictive of local recurrence. Recurrences were more common with nodular melanomas (5.6%) compared to superficial spreading (2.5%) or lentigo maligna melanoma (2.5%), but this difference did not reach statistical significance (P = 0.115). Lower extremity (4.7%) and head and neck lesions (4.4%) recurred more frequently than upper extremity (1.6%) or trunk (1.2%) melanomas (P = 0.0217). The highest recurrence rates were observed in patients with melanomas located on the foot (11.6%) and hand (11.1%). The safety of conservative margins for the excision of low-risk melanomas was demonstrated in a review of 1151 consecutive patients with melanomas less than 1 mm thick where only one local recurrence was observed. Sixty-two percent of these patients had resection margins of 2 cm or less. In 95 patients local recurrence developed as the first site of relapse and were treated with surgical excision. The median survival for this group was 3 years, whereas 20% of this group survived 10 years. These data demonstrate that: (1) the risk of local recurrence rises with increasing tumor thickness, presence of ulceration, and age; (2) melanomas less than 1 mm thick have a very low local recurrence rate, even when excised with margins of 2 cm or less; and (3) local recurrence is a poor prognostic sign because regional and systemic metastases subsequently develop in many patients.

Humans↗
PubMed1985

A human B cell differentiation antigen selectively expressed on mature B cells identified by a monoclonal antibody (HB-2).

A monoclonal IgM antibody (HB-2), produced against a membrane antigen on the Raji, B cell line, reacted by indirect immunofluorescence with 2 to 40% of lymphoblasts from the B cell lines, Raji, Daudi, SN-1036, and SB but not with other types of cell lines, including pre-B, myeloid, melanoma, or T cells. HB-2 antibody reacted with 10 +/- 3% of normal blood mononuclear cells, and was unreactive with monocytes, granulocytes, platelets, or erythrocytes. Two-color immunofluorescence revealed that HB-2 antigen expression was confined to cells bearing surface Ig. An interesting finding was the fact that 25% of plasmablasts induced by pokeweed mitogen also expressed the HB-2 antigen. However, pre-B and plasma cells from normal bone marrow did not express the HB-2 antigen either on their membrane surface or in their cytoplasm. Analysis of 85 leukemias revealed that the HB-2 antigen was expressed on acute and chronic B cell leukemias and Burkitt's lymphomas, but not on malignancies of pre-B, T, myelocytic, or plasma cells. The results suggest that expression of the HB-2 antigen is confined to mature B cells.

Antibodies, Monoclonal↗
PubMed1985

Predicting the risk of abdominal disease in Hodgkin's lymphoma. A multifactorial analysis of staging laparotomy results in 255 patients.

There were 425 consecutive patients treated for Hodgkin's disease at this Medical Center from 1943 to 1983. Of these, 255 patients underwent a staging laparotomy and had complete preoperative clinical records. Overall, 35% had a change in stage (24% were upstaged, 11% downstaged). Twenty-nine per cent of clinical stage I patients were upstaged; 31% of stage II patients were upstaged, while less than 1% were downstaged; and four per cent of stage III patients were upstaged while 44% were downstaged. The diagnostic laparotomy yielded involvement in the spleen in 71% of patients with abdominal involvement, in the periaortic lymph nodes in 41%, in the liver in 11%, and the bone marrow in seven per cent. Only 12% of the 135 patients with negative laparotomies subsequently relapsed in the abdomen after a mean follow-up of 4.8 years. A multifactorial analysis was performed to identify dominant factors predicting the risk for abdominal disease. The factors best predicting abdominal involvement in stage I and II patients were: antecedent symptoms (greater than or equal to 2, 1, 0; p less than 0.00001), histological type [nodular sclerosing (NS) less than lymphocyte-predominant (LP) less than mixed cellularity (MC) less than lymphocyte-depleted (LD); p = 0.0009], and sex (females less than males, p = 0.01). The clinical stage (I vs. II), the site of lymphoma presentation, and the age and race of the patient did not have significant predictive value for the risk of abdominal disease after the other factors were accounted for. A mathematical model was derived for identifying dominant prognostic factors for predicting the risk of abdominal disease in an individual patient setting. The lowest risk patients were asymptomatic females with NS histology (6%) or LP histology (8%), while the highest risk patients were men with multiple symptoms and either MC histology (85%) or LD histology (93%). This information can be useful in making clinical decisions in Hodgkin's lymphoma patients, especially those at an increased risk for surgery.

Hodgkin Disease↗
PubMed1985

Prognostic histopathological factors in malignant melanoma.

An analysis of prognostic factors in 4000 patients with cutaneous malignant melanoma at the Sydney Melanoma Unit and the University of Alabama in Birmingham has demonstrated that the histological features of the primary melanoma become less predictive of survival the more advanced the disease becomes. Thus, whilst 4 features of primary lesions were independent predictors in localized disease (tumour thickness, ulceration, level of invasion and regression), only one of the stronger ones (ulceration) remained predictive in patients with regional lymph node metastases. Once distant spread was evident, there were no parameters of the primary lesion that predicted survival. Thus, in patients with advanced disease prognosis was dictated by the extent of metastatic involvement: the number of positive lymph nodes in stage II patients and the number and location of metastatic sites in stage III patients.

Humans↗
PubMed1985

Cellular immune defects in patients with melanoma involving interleukin-2-activated lymphocyte cytotoxicity and a serum suppressor factor.

Interleukin-2 (IL-2) can stimulate human blood lymphocytes to acquire tumor cytotoxicity, designated as lymphokine-activated killer (LAK) cytotoxicity. In 29 of 33 patients with melanoma, LAK cytotoxicity could be induced with recombinant IL-2 against fresh (noncultured) autologous and/or allogeneic melanoma cells. There was an excellent correlation of LAK cytotoxicity with the clinical stage of disease when the cells were incubated with medium containing IL-2 plus 10% fetal calf serum (p = 0.003). The 14 patients with localized melanomas (group I) had the same level of specific lysis as did 16 normal controls (24% versus 25%). Eleven patients with resectable regional or distant metastases (group II) had a lower level of cytotoxicity compared with normal controls (16% vs 25%), while those with unresectable distant metastases (group III) had the lowest level of cytotoxicity compared with controls (9% versus 25%). When aliquots of lymphocytes from the same patients were cultured with 10% autologous human serum, the levels of LAK cytotoxicity were even lower in patients with localized melanoma and resectable metastases compared with normal controls (15% and 9%, respectively, versus 27% for controls; p = 0.0007). This was due to a serum suppressor factor that inhibited the induction of cytotoxic activity in LAK precursors. The level of cytotoxicity in these patients increased to baseline levels after surgery and the serum suppressor factor disappeared in six of the seven patients in whom it was present before surgery. Thus induction of LAK cytotoxicity requires IL-2, decreases with advancing stages of disease, and is inhibited by a serum suppressor factor related to tumor growth.

Cytotoxicity, Immunologic↗
PubMed1985

Leu-11+ lymphocytes with natural killer (NK) activity are precursors of recombinant interleukin 2 (rIL 2)-induced activated killer (AK) cells.

Precursors of activated killer (AK) cells cytotoxic for human noncultured metastatic melanoma and colon carcinoma were characterized. These cells required 3 days incubation with recombinant interleukin 2 (rIL 2) and DNA synthesis for the induction of AK activity. Both negative and positive cell purification methods were used to identify the subpopulation of cells containing AK precursors. By complement-mediated cell depletion studies, AK precursors were largely present in the Leu-11+ fraction, and to a much lesser extent in the Leu-7+ and Leu-2a+ fractions; they were absent in Leu-3a+ and Leu-4+ cells. Lymphocyte subpopulations were then purified with a cell sorter to positively select for the subset containing AK precursors. Leu-11+ cells had the highest level of AK activity and proliferative response when cultured for 3 days with rIL 2 as well as the highest level of NK activity before culture. Leu-7+ cells had neither AK activity nor a proliferative response when cultured with rIL 2, although they still possessed high NK activity. The same levels of AK and NK activity were found in Leu-2a+ and Leu-2a- fractions, but both activities were absent among Leu-4+ and Leu-3a+ cells. Further fractionation with a two-step sorting technique showed that the highest AK activity resided in the Leu-7-Leu-11+ cell fraction. Morphologically, this subfraction was granular lymphocytes. Titration experiments or rIL 2-responsive cells showed that the number of cells required to achieve a comparable level of rIL 2 proliferative response were as follows: 35 X 10(3) cells from unseparated PBL, 10 X 10(3) cells from Leu-11+ cells, 3.3 X 10(3) from Leu-7-Leu-11+ cells, and 640 X 10(3) cells from Leu-7+ cells. These results indicate that the lymphocyte subpopulation that proliferates in the presence of rIL 2 and then develops AK activity was a subpopulation of Leu-11+ granular lymphocytes, which also possessed the highest NK activity. These Leu-11+ cells lacked the antigens defined by the Leu-7, Leu-3a, or Leu-4 antibodies. Although Leu-7+ cells did not respond to rIL 2 by themselves, they may play a role in the induction of AK activity.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1985

Role of interleukin 2 and a serum suppressive factor on the induction of activated killer cells cytotoxic for autologous human melanoma cells.

Activated killer (AK) cells cytotoxic for freshly prepared autologous melanoma cells were generated in vitro when recombinant interleukin 2 (rIL2) was incubated with peripheral blood mononuclear cells from 11 of 12 patients with metastatic melanoma. The cytotoxic response first appeared significant after 3 days of culture with rIL2; it peaked after 6 days and then declined after 9 days of incubation. Peripheral blood mononuclear cells cultured with medium alone (control) or with recombinant gamma-interferon alone (200 units/ml) failed to acquire AK cytotoxicity at any time in any of the 12 patients. Autologous tumor cells also could not induce AK activity in mixed-lymphocyte tumor cell cultures. The level of AK activity generated was significantly reduced (P less than 0.001) when 10% autologous human serum was used instead of 10% fetal calf serum in the rIL2 cultures. This suppression was specific for the inductive phase of AK activity, because autologous human serum could not suppress the cytotoxic capability of AK cells once they were activated by rIL2. The serum suppressive effect on the induction of AK cytotoxicity could be overcome by increasing the dose of rIL2 or by adding recombinant gamma-interferon to the cultures. Lymphocytes from melanoma patients thus have the latent ability to kill autologous melanoma tumor cells. However, this cytotoxic capability requires an interleukin 2-induced differentiation step that could be amplified by gamma-interferon and inhibited by a serum suppressive factor.

Cells, Cultured↗
PubMed1985

Patients with a deficiency of natural killer cell activity lack the VEP13-positive lymphocyte subpopulation.

Many patients with B-type chronic lymphocytic leukemia (CLL) exhibit a profound defect in their natural killer (NK) cell activity, the basis of which is still obscure. Hence, we analyzed the NK cells from peripheral blood samples from 11 patients with CLL for phenotype and function, after removal of the leukemic cells with a monoclonal antibody (BA-1) plus complement. Phenotypic analysis of these nonleukemic cells with monoclonal antibodies (MoAbs) against NK cells revealed that the CLL patients had higher percentages of HNK-1-positive cells (23.5% compared to controls with 14.7%). In contrast, VEP13-positive cells were absent or low in seven patients (0.8% compared to controls with 11.2%) and normal in four patients (10.5%). When testing NK cell activities against K562 or MOLT 4 target cells, patients with no or minimal numbers of VEP13-positive cells were found to be deficient, while patients with normal percentages of VEP13-positive cells had NK cell activity comparable to controls. Isolation by fluorescence-activated cell sorter of HNK-1-positive cells from patients lacking VEP13-positive cells and NK cell activity indicated that the majority of the HNK-1-positive cells in these patients had the large granular lymphocyte morphology that is characteristic of NK cells. Thus, the deficiency of NK cell activity in CLL patients appears to result from the absence of cells carrying the VEP13 marker.

Antibodies, Monoclonal↗
PubMed1984

Ethnic differences in the lymphocyte proliferative response induced by a murine IgG1 antibody, Leu-4, to the T3 molecule.

The mitogenic effects of isotypically diverse antibodies to the T3 molecule were examined in genetically diverse population groups. Whereas the OKT3 antibody (IgG2a) was mitogenic for blood mononuclear cells from all individuals tested, the 38.1 antibody (IgM) was consistently nonmitogenic. In contrast, studies of the mitogenic effects of the Leu-4 antibody (IgG1) revealed striking ethnic differences. More than 80% of Caucasians and Negroes were good Leu-4 responders, whereas most individuals of Asian origin, including Indian, Japanese, and Chinese, were either Leu-4 nonresponders or Leu-4 low responders. However, the majority of American Indians, as well as a significant minority of Chinese, were good responders. Cell separation studies confirmed that monocytes govern the different mitogenic effects of the anti-T3 antibodies. The results reveal interesting ethnic differences in monocyte accessory function probably mediated via the Fc-gamma receptor, in the stimulation of T lymphocytes by an IgG1 antibody against the T3 molecule.

Adult↗
PubMed1984

Characterization of human granular lymphocyte subpopulations expressing HNK-1 (Leu-7) and Leu-11 antigens in the blood and lymphoid tissues from fetuses, neonates and adults.

Three subpopulations of human granular lymphocytes from blood and lymphoid tissues were characterized using combinations of the monoclonal antibodies (mAb) HNK-1 (Leu-7), Leu-11 and VEP13. Each subpopulation was confirmed to possess natural killer (NK) cell functional capability, but a different level of cytotoxic efficiency (HNK-1+leu-11- less than HNK-1+Leu-11+ less than HNK-1-Leu-11+). In adult from 23 healthy donors, the subpopulations with HNK-1+Leu-11-, HNK-1+Leu-11+ and HNK-1-Leu-11+ phenotypes comprised 4.7 +/- 3.0, 8.0 +/- 6.4 and 3.9 +/- 3.5% of mononuclear cells, respectively. Despite their distinct surface marker phenotypes and NK functional ability, all 3 subpopulations exhibited granular lymphocyte morphology. One of these subpopulations, HNK-1+Leu-11-, also expressed the pan-T cell antigen Leu-4. Different patterns were observed in fetal bone marrow and cord blood, where the vast majority of HNK-1+ cells lacked the Leu-11 antigen (HNK-1+Leu-11+ cells). The HNK-1 antigen was not expressed on granulocytes and their precursors, whereas both Leu-11 and VEP13 antigens were expressed on these myeloid cells from fetal bone marrow and cord blood as well as adult bone marrow and spleen. Cell lines of granular lymphocytes cultured in the presence of interleukin 2 all possessed the HNK-1+Leu-4+ phenotype and NK functional capability but lacked the Leu-11 and VEP13 antigens on their surface after 15 days of culture. Although granular lymphocytes expressing the Fc receptors reacting with the mAb Leu-11 and VEP13, are the most functionally active NK cells, the HNK-1+ subpopulation lacking the Leu-11 and VEP13 antigens appears to be an important population (possibly an immature form of granular lymphocytes) for delineating the cell lineage(s) and differentiation of human granular lymphocytes. Although none of the currently available mAb react both inclusively and exclusively with human granular lymphocytes, the combination usage of these antibodies permits a more precise and comprehensive analysis of these subsets.

Adolescent↗
PubMed1984

Antigenic determinant(s) shared by the human Thy 1 and human IgG.

A human T cell differentiation antigen (p25) previously described as being the mouse theta equivalent has been examined for shared antigenic determinants with immunoglobulin. A strong cross-reactivity of an antiserum prepared against p25 antigen was established with human IgG subclasses. This antiserum does not react with human IgM or IgA, nor with primate immunoglobulins. The shared determinants appear to be associated with the disulphide-bonded cysteines in the first and third constant domains of the IgG molecule and the 9-112 disulfide bond of Thy 1.

Antibody Specificity↗