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Biomedical subjects

R F Irie

Publications and source records attributed to R F Irie.

At least 91 records · Page 5Linked to original sources
PubMed1982

Identification of a human neuroectodermal tumor antigen (OFA-I-2) as ganglioside GD2.

Two monospecific human antibodies (anti-OFA-I-1 and anti-OFA-I-2) produced in vitro by lymphoblast cell lines originating from melanoma patients have been shown previously to recognize cell surface antigens (OFA-I-1 and OFA-I-2) on human tumors and fetal brain: OFA-I-1 is expressed on a variety of human tumors, while OFA-I-2 has been detected only on tumors of neuroectodermal origin. Evidence presented in this report suggests that the two antigens expressed by a cultured human melanoma cell line (M14) are chemically distinct and that OFA-I-2 is a cell surface glycolipid, ganglioside GD2: GalNAc beta 1 leads to 4 NeuAc alpha 2 leads to 8NeuAc alpha 2 leads to 3 Gal beta 1 leads to 4Glc-ceramide.

Antibodies, Monoclonal↗
PubMed1982

Humoral immune response to intralymphatic immunotherapy for disseminated melanoma: correlation with clinical response.

Since September 1979, 44 stage III melanoma patients treated with intralymphatic immunotherapy (ILI) with an oncofetal antigen (OFA-I)--enriched tumor cell vaccine (TCV) had evaluable humoral immune responses and clinical follow-up. Fourteen patients (32%) had stabilization or regression of tumors or remained free of resected disease. The median survival was 17 months, compared with 6 months for controls (P less than 0.001). Humoral immune responses were monitored by immune adherence using an OFA-positive human melanoma cell line, M14, as target. Alloantibodies were removed by absorption with L14 lymphoblasts autologous to M14. Twenty-two patients (50%) developed elevated antibody titers within 4 months, and 12 of the 22 (55%) had no disease progression. In contrast, 20 of 22 patients (91%) who failed to develop elevated titers had disease progression (P less than 0.01). The median titer was significantly higher during the first 4 months in the group whose disease did not progress (P less than 0.04). This study demonstrated that ILI with allogeneic OFA-I-enriched TCV can induce objective tumor regression and prolonged survival in patients with disseminated melanoma. Furthermore, because the specific humoral immune response correlates with clinical results, immunization efficacy can be monitored within a short period of time, which should aid future efforts to achieve optimal immunotherapy.

Adult↗
PubMed1981

Oncofetal antigen-I: distribution in human tumors.

Oncofetal antigen-I (OFA-I) is a human tumor-associated fetal antigen that cross-reacts with fetal brain. The biological distribution of this antigen was studied in a variety of histologic types of human tumors and normal tissues. A total of 170 human tumors and 89 normal tissues obtained from biopsied and autopsied specimens were tested by immune adherence absorption assay. The antigen was most prevalent in malignant melanomas (82%); next in order of incidence were lung carcinomas (71%), sarcomas (61%), brain tumors (58%), and breast carcinomas (53%). However, OFA-I was found in only 15% of gastrointestinal tumors. The four hepatoma specimens tested were negative for OFA-I. OFA-I was also present in metastases and normal-appearing tissues of patients with OFA-I positive tumors but was not found in normal tissues from noncancer patients. These studies demonstrated that OFA-1 is widely distributed among human tumors. It appears to be more prevalent in tumors of ectodermal and mesodermal origin.

Antigens, Neoplasm↗
PubMed1981

Prolonged survival for melanoma patients with elevated IgM antibody to oncofetal antigen.

Antibody directed against a cultured melanoma cell line known to express an oncofetal antigen was measured in sera obtained from patients with stage II melanomas. This study was undertaken to determine if an inhibiting or enhancing effect on tumor growth would be suggested by a positive or negative correlation of antibody levels with tumor recurrence or patient survival. A positive correlation with disease-free interval and survival was detected among patients who had high levels of the IgM class of antibody before and shortly after surgery for state II disease. The IgG class of antibody over the period measured did not correlate consistently with tumor recurrence. Absorption of the IgM antibody with fetal brain confirmed that the dominant detectable reactivity was directed to the oncofetal antigen. The relevance of these findings is related to that of other evidence indicating that immunity to fetal antigens expressed on tumor cells is a participant in host-tumor interaction.

Antibodies, Neoplasm↗
PubMed1980

Natural humoral immunity in patients with malignant disease.

In order to assess the association of enhancement or suppression of humoral immune responses with cancer histology, sera from age and sex matched patients with sarcoma, melanoma and breast cancer and from normal donors were tested for natural antibodies in six serologic assays. Patients with melanoma were found to have a significantly higher level of antibody than the other groups tested. Antibody levels in patients with breast cancer were lowest.

Adult↗
PubMed1980

Immunologic aspects of unknown primary melanoma.

Immune responses of 36 patients with stage II unknown primary melanoma were compared to those of 83 stage II patients with known primary melanoma. The two groups of patients were similar in age, sex, and extent of disease. Delayed cutaneous hypersensitivity to dinitrochlorobenzene (DNCB) was nearly identical in both groups. Patients with unknown primary melanoma had a mean level of reactivity of 4.7 +/- 0.37 and the patients with known primary had a mean level of 5.0 +/- 0.17. Of unknown primary patients 4.2% were unreactive to DNCB and 4.8% of known primary patients were unreactive. Antibodies to cultured melanoma cells were slightly more prevalent in serum from the unknown primary patients (67%) than from known primary patients (45%), but mean titer of positive sera did not differ significantly. Lymphoproliferative assays did not demonstrate differences in lymphocyte reactivity among the two groups when tested with Concanavalin A, mixed leukocyte culture, or unstimulated lymphocyte blastogenesis. No differences could be detected in these assays of humoral and cellular immune responses when patients with unknown primary melanoma were compared to those with known primary melanoma and similar clinical characteristics.

Adult↗
PubMed1980

A serologic study of cultured breast cancer cell lines: lack of antibody response to tumour specific membrane antigens in patients.

Humoral antibodies to tumour associated membrane antigens of cultured human breast cancer cell lines were studied using the immune adherence (IA) test. Sera from 353 post-operative breast cancer patients and from twenty-five patients immunized by allogeneic breast cancer cells were tested against the MDA-MB-436 cell line. Fifty-five (15.6%) sera samples from the non-vaccinated group and 131 (77.3%) of 168 sera samples from the immunotherapy group were IA-positive to this cell line after absorption with bovine erythrocytes to exclude antibody to heterologous membrane antigens (HM Ag). Forty-five of the 55 positive-sera from the non-immunized group and 113 of the 131 positive sera from the immunized group became IA-negative after further absorption with lymphoblastoid cells autologous to MDA-MB-436. Subsequently, the twenty-eight positive sera remaining sere tested for oncofetal antigens (OFA). After absorption with OFA rich tissues (fetal brain and M14 melanoma cells), no reactivity remained in the sera samples. In order to identify antibodies specific to breast cancer antigens, the 129 sera samples from non-immunized patients were tested against four other breast cancer cell lines; MDA-MB-157, MDA-MB-231, MCF-7 and UCLASO-B1. Four sera which reacted to more than three of the cell lines were identified. The reactivity of three of the four was due to anti-OFA antibody. The last serum sample was reactive to anti-HLA antibodies. These results indicate that sera of patients with breast cancer contain antibodies to OFA, but do not detect breast histologic type specific antigens as tested by IA using five breast cancer cultured cell lines.

Antibodies, Neoplasm↗
PubMed1979

Oncofetal antigen: a tumor-associated fetal antigen immunogenic in man.

Oncofetal antigen (OFA) has been defined with the use of human natural antibodies as a membrane antigen of human cancer cells that cross-reacts with human fetal brain tissues. The immunogen that elicits the antibody is unknown. The present study was undertaken to examine the immunogenicity of the OFA found on tumor cells. Postoperative melanoma patients were immunized with OFA-positive melanoma cells. Anti-OFA reactivities in the immunized sera were titrated by the immune adherence assay with the use of a known OFA-positive cultured melanoma cell line, M14, as target cell. Alloantibodies were excluded by absorption with lymphoblastoid cells autologous to M14. Anti-OFA antibody then was identified by absorption with fetal brain. In 6 months of immunization, 19 of 23 patients produced increased anti-OFA antibodies. The peak titers ranged from 1:16 to 1:2,048. Sera from 18 patients who were not immunized also were tested for 6 months postoperatively, and none had significant increases in antibody titers. The increase of anti-OFA antibody titer in response to the immunization with OFA-positive tumor cells suggests the immunogenic capability of tumor-related OFA in man.

Antibodies, Neoplasm↗
PubMed1978

Establishment of paired tumor cells and autologous virus-transformed cell lines to define humoral immune responses in melanoma and sarcoma patients.

Peripheral blood lymphocytes and skin fibroblasts from 12 cancer patients were infected with Epstein-Barr virus (EBV) or SV40 virus. The EBV-transformed lymphoblasts and SV40-transformed fibroblasts were grown as continuous cell lines and expressed the same histocompatibility antigens as tumor cell lines established from the same cancer patients. Sera from 350 melanoma and 195 sarcoma patients were tested for antibody reactive with membrane antigens on three of these tumor cell lines (two melanomas and one sarcoma) by immune adherence (IA) and indirect immunofluorescence (IMI) assays. Antibodies to HLA and other non-tumor-related antigens were completely removed from the most reactive sera by quantitative absorption with 4 x 10(7) lymphoblasts or 10(7) transformed fibroblasts autologous to the tumor target cells. These paired cell lines were used to monitor humoral immune responses in melanoma and sarcoma patients receiving allogeneic tumor cell vaccines.

Antibodies, Neoplasm↗
PubMed1978

A new heterophile antigen: man distinguished from higher apes and other mammals.

Human cell membranes acquired an antigenic substance from the bovine serum in culture medium. The antigen was named the heterologous membrane antigen (HM Ag). Cross-reactive antigen was found in sera of all mammals tested, except for man. The distribution of the HM Ag serologically distinguished man from other mammals.

Animals↗
PubMed1977

Expression of histocompatibility (HLA) antigens on tumor cells and normal cells from patients with melanoma.

The expression of HLA antigens and beta2-microglobulin (beta2-mu) on cultured melanoma cells originated from 11 patients has been quantitated and compared with that on fibroblasts and cultured human lymphoid cells originated from the same patients. No qualitative or quantitative difference was detected with the exception of one melanoma line. HLA antigens were also quantitated in sera from melanoma patients: two sera reacted with anti-HLA-B7 antibodies although this specificity was not expressed on lymphocytes from whom the sera were obtained. A technique to quantitate HLA antigens on cells developed in the course of this study is described.

Cell Membrane↗
PubMed1976

Human tumor cells grown in fetal calf serum and human serum: influences on the tests for lymphocyte cytotoxicity, serum blocking and serum arming effects.

Peripheral blood lymphoid cells (PBL) from cancer patients and normal donors were tested against three melanoma cell lines grown in either 10% fetal calf serum (FCS) or 2.5-5% human AB serum in order to determine if the heterologous membrane (HM) antigen or other FCS antigens acquired from the bovine serum supplement could influence lymphoid cell-mediated cytotoxicity in vitro. FCS-grown melanoma cells were more susceptible than the AB serum-grown subline to lymphocyte cytotoxic effects. Arming effects by autologous sera on normal donor lymphocytes and to a lesser extent on lymphocytes of cancer patients were more pronounced on the FCS-grown M12 melanoma cells. This effect was abrogated when the cells were grown in human AB serum for at least 8 weeks. The non-HM tumor-associated antigen remained at the same original low level. Blocking effects were more evident on the AB-grown M14 melanoma line. These data suggest that the FCS antigens on the cell surface may have been responsible for the augmented PBL cytotoxicity. The anti-FCS antibody present in normal and cancer patients' blood induced an antibody-dependent cellular cytotoxicity (ADCC). Elimination of arming activity against HM or other FCS antigens from AB-grown cells may have made the serum blocking factors more apparent. However, cytotoxicity against tumor cells by PBL from normal donors was still apparent even on the human serum-grown cells, suggesting that a different antigen-antibody system was also responsible for this "non-specific" activity.

Animals↗
PubMed1976

A membrane antigen common to human cancer and fetal brain tissues.

Membrane antigens of a cultured human melanoma line, UCLASO-M14, were studied using immune adherence techniques. Allogeneic sera from melanoma patients that were reactive with the M14 but nonreactive with lymphoid cells of the M14 donor were used as antibodies. The antigen responsible for the reaction between M14 and the antibodies was searched for in other cancer, normal, and fetal tissues using antibody absorption techniques. The antigen was found in a variety of different histological types of biopsied and cultured cancer cells as well as in melanomas. The antigen did not exist in biopsied normal tissues, but it appeared in cultured normal skin and muscle. Neither normal lymphocytes nor cultured lymphoid cells showed any antigenicity. The antigen was present in human fetal tissues and was the strongest in fetal brain tissues at 22 weeks of development. Liver, spleen, thymus, and small intestine from the same fetus were negative for antigen.

Antigens, Neoplasm↗
PubMed1975

Detection of antibody and complement complexed in vivo on membranes of human cancer cells by mixed hemadsorption techniques.

The mixed hemadsorption (MHA) techniques demonstrated antibody and complement fixed in vivo to the surface of human cancer cells. Tumors from 12 cancer patients and normal tissues from 5 cancer patients and 8 patients with cerebrovascular or cardiac diseases were collected from biopsy and autopsy for in vitro testing. Antiserum to human whole immunoglobulins and antiserum to human C3 were used in the MHA techniques. Positive MHA patterns were demonstrated on the surface of cancer cells by both methods. Positive reactions ranged from 12 to 32% in mixed hemadsorption for anitbody detection and from 10 to 34% in mixed hemadsorption for complement component 3 detection. Normal tissues obtained from cancer patients or from patients who died of causes other than cancer rarely exhibited distinct MHA reactivity. Collectively, the data suggest that most human cancers are antigenic in the autologous host and that tumor-associated antigens of cancer cells react in vivo with their humoral antibody to fix complement.

Antibodies, Neoplasm↗