Mouse monoclonal IgM antibody against human lung cancer line SK-LC-3 with specificity for H(O) blood group antigen.

Spleen cells from mice immunized with the human lung cancer line SK-LC-3 were fused with mouse NS-1 myeloma cells. One of the hybrid clones produced a monoclonal IgM antibody (designated F-3), detected with antimouse Ig-MHA and hemagglutination assays. This antibody was completely absorbed by O red cells and completely inhibited by low concentrations of H(O) glycoproteins and hog mucin (A + H).

Heterogeneity in surface antigen and glycoprotein expression of cell lines derived from different melanoma metastases of the same patient. Implications for the study of tumor antigens.

Three established lines of melanoma cells were derived from anatomically distinct metastases occurring in a single patient (DX). The lines, DX-1, DX-2, and DX-3, showed marked phenotypic diversity, as indicated by characteristic differences in growth rate, morphology, pigmentation, and the expression of surface antigens and glycoproteins. DX-1 and DX-3 expressed HLA-DR products, whereas DX-2 lacked HLA-DR expression.

Treatment of acute nonlymphocytic leukemia in adults: response to 2,2-anhydro-1-B-D-arabinofuranosyl-5-fluorocytosine and thioguanine on the L-12 protocol.

Fifty-one adult patients with acute nonlymphocytic leukemia (excluding acute promyelocytic leukemia) were treated on the L-12 protocol. The L-12 differed from the preceding L-6 in that 2,2-anhydro-1-B-D-arabinofuranosyl-5-fluorocytosine (AAFC), replaced arabinosylcytosine (ara-C) together with 6-thioguanine (TG) for remission induction. Achievement of remission was followed by an extended 14-week multi-drug consolidation program.

Cell surface antigens of human renal cancer defined by mouse monoclonal antibodies: identification of tissue-specific kidney glycoproteins.

Seventeen monoclonal antibodies derived from fusions with spleen cells of mice immunized with established culture lines of renal cancers identified nine cell-surface antigenic systems. Six of the systems (gp160, S25, gp120r, gp120nr, gp115, and V1) represent antigens not previously described. The other three systems are related to HLA-A, -B, and -C heavy chain and A and B blood group antigens.

Surgical adjuvant therapy of malignant melanoma with corynebacterium parvum.

The authors' previous surgical adjuvant trial in patients with malignant melanoma at high risk of recurrence has shown no difference in disease-free interval or survival between patients randomized to surgery + BCG or surgery alone. Reported here is a subsequent nonrandomized trial in 30 similar patients who received surgery + Corynebacterium parvum (CP) 4 mg I.V.

Immunologic aspects of cancer.

Work in progress should produce within the next few years a better understanding of the nature of immune responses to human cancer antigens. Studies to date, notably with melanomas, have shown that many, perhaps most, are immunogenic. However, the antibodies elicited are often not specific to tumor antigens.

DNCB reactivity and prognosis in 419 patients with malignant melanoma.

Delayed cutaneous hypersensitivity to 2,3-dinitrochlorobenzene (DNCB) was tested in 419 patients with malignant melanoma to determine whether DNCB reactivity was associated with prognosis. At the time of definitive surgery, a positive DNCB test was seen in 82% of the patients in State I (regional lymph node histologically negative) and in 81% of patients in Stage II (regional lymph node positive). A positive DNCB test, obtained at the time of staging in patients with more advanced disease, was seen in 70% of patients in State III (metastases in, at most, on internal organ) and in 68% of patients in Stage IV (metastases in more internal organ).

Automated flow cytometry to monitor intravesical BCG therapy of superficial bladder cancer.

The automated flow cytometry system (FCM) at Memorial Sloan-Kettering Cancer Center has been used to monitor the effect of intravesical BCG in the therapy of superficial bladder cancer. Analysis of saline bladder washings prior to therapy, weekly during the six weeks of therapy, and at follow-up examination in 2 patients, 1 responder and 1 nonresponder, provides the basis for some projections regarding the potential value of this technique.

Immunotherapy with oral BCG and serial immune evaluation in childhood lymphoblastic leukemia following three years of chemotherapy.

Thirty-nine children with ALL who had completed three years of chemotherapy were randomized to receive oral BCG for immunotherapy or no treatment as controls. There was not a significant difference between the two groups in the relapse rate. Among the immune parameters, only in vitro blastogenic responses to PHA and PPD rose significantly in the BCG group compared with the controls.

Cell surface antigens of human malignant melanoma: definition of six antigenic systems with mouse monoclonal antibodies.

Eighteen mouse monoclonal antibodies were selected for reactivity with cell surface antigens of the immunizing human melanoma cell line SK-MEL-28. Six distinct antigenic systems were defined by direct serological assays and absorption tests with a panel of 41 cell lines derived from normal and malignant human tissues. Biochemical analysis indicated that two of the antigens are glycoproteins with molecular sizes of 95,000 and 150,000 daltons (gp95 and gp150).

Serological survey of normal humans for natural antibody to cell surface antigens of melanoma.

Sera of 106 normal adult men were tested for antibodies reacting with cell surface antigens of three established lines of cultured malignant melanoma. Positive reactions with a protein A assay for IgG antibodies were extremely rare (1-2%). The frequency of positive reactions with assays for IgM antibodies was higher: 5-15% in immune adherence assays and 55-82% in anti-C3 mixed hemadsorption assays.

Alloantigen-induced T-cell proliferation: Lyt phenotype of responding cells and blocking of proliferation by Lyt antisera.

Cytotoxic T cells of the mouse express Lyt-1 as well as Lyt-2 and -3 on their surface, and T-cell cytotoxicity can be blocked by Lyt-2 and Lyt-3 (but not Lyt-1) antisera in the absence of added complement [Nakayama, E., Shiku, H., Stockert, E.

Immunotherapy of colon cancer: prospects for developing immunogenic vaccines based on autologous serological typing.

Exploration of specific immunization as a means of cancer therapy has been hampered by the lack of knowledge of human cancer antigens. Recent progress in the serological definition of cell surface antigens of malignant melanomas, renal cancers, and astrocytomas provides a new basis for the construction of immunogenic vaccines and their clinical testing. Application of the same approach to colon cancer depends on the development of methods which permit continuous growth of colon cancer cells in tissue culture.

Genetically appropriate expression of HLA and DR (IA) alloantigens on human melanoma cell lines.

Studies of the expression of HLA and DR alloantigens on cultured human melanoma cells in comparison with those expressed on peripheral lymphocytes and B-cells derived from the same patients have shown that the HLA-A,B, and C locus antigens expressed on the cultured tumor cells were consistent with those expected from the typing of peripheral blood lymphocytes. One melanoma cell line failed to express all the HLA antigens expected from donor typing. All five of the lines tested also expressed DR antigens and in three instances these could be demonstrated to have genetically consistent allotypes.

Effect of short-term levamisole therapy on delayed hypersensitivity.

A randomized trial of short-term Levamisole treatment was undertaken in a cancer population unresponsive to dinitrochlorobenzene (DNCB) to determine whether this agent increased delayed hypersensitivity. Of 100 patients entered, 50 received Levamisole (150 mg daily x 3) during DNCB challenge. The other 50 patients were challenged but not given the drug.

Endotoxin-induced tumor necrosis factor.

The serum of BCG-infected mice treated with endotoxin contains a substance (tumor necrosis factor, TNF) which mimics the tumor-necrotizing action of endotoxin itself. TNF is not residual endotoxin, but a factor released from host cells, probably macrophages. TNF induced in the same way in rats and rabbits also causes necrosis of transplanted murine tumors.

Tumor-specific antigens.

Based on autologous serological typing of cultured astrocytoma cells from 30 patients, three classes of surface antigens have been defined. Class I antigens are restricted to autologous astrocytoma cells. Class II antigens are shared by autologous as well as certain allogeneic tumors, but are not detected on normal cells.

Cell surface antigens of human renal cancer defined by autologous typing.

Sera from 28 patients with renal cancer were tested for reactivity with surface antigens of cultured autologous renal cancer cells. Four serological assays were used to survey sera for autologous antibody. Immune adherence, protein A, and C3-mixed hemadsorption assays detected reactivity in a high percentage of patients (80-100%), whereas mixed hemadsorption assays were negative with sera from all but one patient.

Cell-mediated cytotoxicity for cultured autologous melanoma cells.

Peripheral blood lymphocytes from 32 patients with malignant melanoma were tested for cell-mediated cytotoxicity (CMC) against cultured autologous melanoma cells. Effector cells were prepared from venous blood by defibrination, gel sedimentation, nylon column filtration, and lysis of remaining erythrocytes with NH4Cl. Melanoma cells prelabelled with [3H])proline were used as target cells in a 40-h assay and CMC was evaluated against standards obtained with blood lymphocytes from the least reactive normal donor.

Definition of a unique cell surface antigen of mouse leukemia RL male 1 by cell-mediated cytotoxicity.

BALB/c x-ray-induced leukemia RL male 1 is strongly immunogenic for (BALB/c x C57BL/6)F1 mice. Transplants of RL male 1 regressed after initial growth, and after tumor regression mice could resist repeated inocula of 10(7) RL male 1 cells. Spleen cells from immunized mice after in vitro stimulation with RL male 1 were cytotoxic for RL male 1 cells in 3-hr 51Cr assays.

Cytotoxic T cells: Lyt phenotype and blocking of killing activity by Lyt antisera.

WE REEXAMINED TWO QUESTIONS CONCERNING LYT ANTIGENS OF CYTOTOXIC T CELLS OF THE MOUSE: is Lyt-1 antigen expressed on cytotoxic effector cells and can cytotoxicity be blocked by antibody to Lyt antigens in the absence of added complement? A 3-hr (51)Cr-release assay with splenic effector cells and leukemia or myeloma target cells was used to measure cell-mediated cytotoxicity. The cytotoxic activity of effector cells against allogeneic targets was abolished by exposure to Lyt-1, Lyt-2, or Lyt-3 antiserum and complement. Specificity was established by tests with C57BL/6 Lyt congenic mice and absorption studies with thymocytes.