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Biomedical subjects

I Hellström

Publications and source records attributed to I Hellström.

At least 181 records · Page 10Linked to original sources

Tumor-enhancing suppressor activator T cells in spleens and thymuses of tumor immune mice.

Cells from the spleens and thymuses of BALB/c mice whose Moloney sarcoma virus (MSV)-induced, primary sarcomas have regressed 2-3 months earlier ("MSV regressors") or are in the process of regressing can, when adoptively transferred to syngeneic mice given MSV at the age of 20 days, prevent the natural regression of the MSV sarcomas in the recipient mice. The cells responsible for this tumor-enhancing effect express the Thy 1 marker. They are not demonstrable in the thymuses of normal untreated mice or in mice that have either been immunized against or are bearing methylcholanthrene-induced sarcomas. The tumor-enhancing cells are not destroyed after administration of 400 rads (1 rad = 1.00 x 10(-2) J/kg) of whole body radiation. However, the effect of the irradiated cells is seen only in the presence of a nonirradiated T-cell population, represented in the thymuses of normal control mice, with which we postulate that they interact. Studies on a transplantable, chemically induced, murine leukemia virus antigen-negative sarcoma, MCA-1460, further support the concept that relatively radioresistant thymus cells from immune mice can enhance tumor outgrowth by interacting with radiosensitive T cells that are present in nonimmune mice.

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Cell surface antigens of human melanoma identified by monoclonal antibody.

Mouse NS-1 myeloma cells were fused with spleen cells from mice that had been immunized with cells from a human melanoma, M1804. Hybrid cells were grown in selective medium and tested for production of antibody to surface antigens of M1804 cells. Three hybrids that produced antibodies that bound to the melanoma cells but not to autologous skin fibroblasts were cloned. Antibodies produced by two of the clones were cytotoxic to M1804 cells in the presence of rabbit complement. Extensive specificity tests showed that the antibodies produced by the clones bound strongly only to M1804 cells; significant, although weaker, binding occurred with 2 of 11 allogeneic melanomas. Apart from weak binding of the antibody produced by one of the clones to a breast carcinoma, binding assays of five carcinomas, one sarcoma, and fibroblasts from 17 individuals were negative, as were cytotoxic tests of 10 lymphoblastoid cell lines and peripheral blood lymphocytes from 68 normal donors and 12 chronic lymphocytic leukemia patients. This suggests that we have identified one or more determinants of a melanoma-associated antigen(s), whose expression is limited to a small proportion of melanomas.

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Antitumor effect of whole-body X-irradiation: possible role of an X-ray-sensitive T suppressor cell population.

Findings have been presented which support the concept that SBF and suppressor cells can modify immune responses to tumor antigens in vivo, and they indicate that some types of SBF act through a radiosensitive suppressor cell system. We believe that further understanding of the mechanisms involved will provide methods of manipulating the immune response to certain immunogenic tumors and may thereby help in the development of tumor immunotherapy.

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Selective localization of radiolabeled immune lymphocytes into syngeneic tumors.

Newly formed long-lived small lymphocytes (LLSL) generated during the immunization of mice to tumor specific transplantation antigens (TSTA) of syngeneic MCA-induced sarcomas were labeled. We then studied the localization of these labeled cells into tumor implants. "Crisis-cross" experiments were performed in which MCA sarcomas with individually distinct TSTA were studied in parallel. A selective localization of LLSL into tumors to which the lymphocytes were immune was found when small tumor pieces were implanted into immune mice whose LLSL had been labeled. Selective localization was also detected upon adoptive transfer of immune LLSL to tumor-bearing mice, but only when these mice had, before transfer, received a sublethal dose of whole body irradiation.

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The need to establish whether the leukocyte adherence inhibition test is a reliable assay of tumor immunity in humans.

Lymphocytes from human cancer patients can react to tissue-type-specific antigens shared by many tumors of the same histological type and different for tumors of different types. Such reactions have been detected, for example, by using microcytotoxicity assays and leukocyte migration inhibition techniques. Work presented at this workshop indicates that the leukocyte adherence inhibition test is an excellent assay for detecting reactivity to antigens shared by neoplasms of the same histological type. However, very little is known of the nature of these antigens; for example, we do not know whether they are tumor specific or just normal tissue antigens. The usefulness of the leukocyte adherence inhibition test for patient monitoring and for diagnostic purposes also needs to be studied more.

Antigens, Neoplasm↗

Regression and inhibition of sarcoma growth by interference with a radiosensitive T-cell population.

BALB/c mice were inoculated subcutaneously with 10(6) cells from either of two syngeneic sarcomas 1315 and 1425. 6--8 days later, the mice were randomized into groups which were left untreated or given 400 rads of whole body irradiation. Irradiation significantly retarded the growth of both sarcomas, and complete regressions were seen of approximately equal to 30% of the small, established 1315 tumors. The anti-tumor effect of irradiation was abolished if the irradiated mice were inoculated with a T-cell-enriched (but not with a T-cell deprived) suspension of syngeneic spleen cells, suggesting that the irradiation inhibited tumor growth by affecting a radiosensitive population of host suppressor T cells.

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Unique and common tumor-specific transplantation antigens of chemically induced mouse sarcomas.

Methylcholanthrene-induced sarcomas of BALB/c mice express unique tumor specific transplantation antigens (TSTA), and weaker, common TSTA. Antigens of endogenous murine leukemia virus (MuLV) expressed by some of these tumors cannot completely account for these common TSTA. However, MuLV antigens on the immunizing tumor appear to increase the immunogenicity of the common TSTA.

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A highly sensitive and reproducible microcytotoxicity assay for demonstrating cytotoxic antibodies to cell surface antigens.

An assay is described, in which target cells are suspended in diluted rabbit serum (as a source of complement) and pipetted into the wells of Falcon No. 3034 Microtest plates, to which diluted antiserum (or control serum) has been added. After 18--24 h of incubation, the plates are stained with crystal violet and counted using an electronic Quantimet image analyzer. This technique could reproducibly detect complement-dependent cytotoxic antibodies to target cell H-2 antigens and to MuLV gp70 on cell lines which expressed this antigen, at serum dilutions up to 1:160,000. The cytotoxic antibodies could be removed by absorption of sera with cells carrying the respective antigens.

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An isotope-release assay and terminal-labeling assay for measuring cell-mediated allograft and tumor immunity to small numbers of adherent target cells.

A 51Cr-release assay and terminal 51Cr-labeling assay for measuring cell-mediated immunity to adherent target cells is described. Both techniques utilize small 10 microliter-per well microtiter plates, require low numbers of target cells (50-500 per well), and consequently, relatively small numbers of effector cells per well (3x10(3) -1x10(5)). Both assays are objective, quantitative, and simple to perform. The suitability of these techniques for monitoring immunologically specific, cellmediated, cytotoxic response to syngeneic and allogeneic tumor cells and normal skin fibroblasts is demonstrated. Lymph node cells, spleen cells and peritoneal exudate cells serve as effectors.

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Radioimmunoassay of murine leukemia virus p30 using Staphylococcus aureus as immunoadsorbent.

A competition radioimmunoassay for murine leukemia virus p30 has been developed. Serial dilutions of the unknown in wells of microtiter plates are incubated with 125I-labeled p30 and goat antiserum specific for p30. Bound p30 is then removed by an immunoadsorbent specific for goat immunoglobulin, prepared from S. aureus. An internal standard of 51Cr is used to correct for volumetric errors, the amount of the labeled p30 precipitated being calculated from the 125I/51 Cr ratio of the supernatant. The assay is rapid, being completed within 2 h, precise, having a coefficient of variation less than 1%, and sensitive, being capable of detecting p30 concentrations as low as 2 ng/ml in a volume of 0.02 ml. It has been used to measure p30 levels in a series of MCA-induced fibrosarcomas of BALB/c mice.

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Evidence that tumor antigens enhance tumor growth in vivo by interacting with a radiosensitive (suppressor?) cell population.

The growth of a small number of cells from each of two chemically induced BALB/c sarcomas was enhanced when x-irradiated (15,000 rads) cells of the same sarcoma were mixed with the tumor inoculum. This enhancement did not occur if the recipients had been given a total body x-irradiation of 450 rads. Tumor neutralization (Winn) tests showed that tumor cells irradiated in vitro enhanced tumor growth only in the presence of radiosensitive cells present in the spleens of both nonimmune and tumor-bearing mice. On the basis of these findings we postulate that tumor antigen blocks effective tumor immunity by a mechanism that involves a suppressor cell population.

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Antibody response of mice to chemically induced tumors.

BALB/c mice immunized with syngeneic methylcholanthrene-induced fibrosarcomas did not have antibodies against the unique tumor-specific transplantation antigens, even though they were capable of rejecting a lethal dose of tumor cells. Endogenous murine leukemia virus antigens expressed by certain of the tumors did, however, elicit high titers of antibodies, accounting for serological crossreactions that occurred between those tumors.

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