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Biomedical subjects

A L Grossberg

Publications and source records attributed to A L Grossberg.

At least 19 recordsLinked to original sources

A tumor-associated organ-specific antigen characteristic of spontaneously metastatic rat mammary carcinomas.

An organ-specific tumor-associated antigen (TAA) was present in several metastatic and nonmetastatic mammary carcinomas induced in WF female rats by 3-methylcholanthrene. The level of TAA was high in 2 metastatic carcinomas tested (TMT-081 and SMT-2A) and much lower--by a factor of 50--200--in 2 nonmetastatic mammary carcinomas (MT-100 and MT-W9B). The TAA in the 2 metastatic tumors was identical, as demonstrated by immunodiffusion and supported by cross-reactivity with antibody against TAA from TMT-081 in a binding inhibition radioimmunoassay. The TAA was shed in relatively large amounts by the metastatic tumors maintained in short-term organ culture. The high level and shedding of TAA thus appeared to be characteristics of the metastatic tumors but not of the nonmetastatic ones. This suggests that TAA on the cell membrane or in the circulation may be involved in the metastatic process as a factor blocking potentially cytotoxic cells or in other ways leading to suppression of the immune response against the tumor.

Animals

Carcinoembryonic antigen-binding immunoglobulin isolated from normal human serum by affinity chromatography.

A human immunoglobulin that binds carcinoembryonic antigen (CEA) was isolated from four individual normal human sera by affinity chromatography with the use of a CEA-Sepharose solid adsorbent. The yield of isolated protein, termed human CEA-binding protein (HCBP), ranged from 1.8 to 10 microgram/ml serum. HCBP is a gamma-globulin of restricted electrophoretic heterogeneity as shown by immunoelectrophoresis. HCBP was shown to bind radioiodine-labeled CEA both by a radioimmune precipitation assay and by a radioimmunoelectrophoresis assay. This protein was of practical interest because of its potential usefulness as a carrier of radioactivity or therapeutic agents to a CEA-producing tumor for therapeutic or diagnostic purposes.

Antibodies, Neoplasm

Identification of heavy chain tyrosine 33 in the binding site of myeloma protein McPC 603 by paired label iodination.

The phosphorylcholine binding mouse myeloma protein McPC 603 has been shown to have tyrosyl residues in its binding sites by the fact that iodination of the protein causes extensive loss of binding activity which can be substantially retained when the protein is iodinated with sites occupied by ligand. Paired label iodination of McPC 603 protein allowed identification of the tyrosine involved and showed the tyrosine to be in the heavy chain. Gel filtration of heavy chain peptides enabled the tyrosyl-containing peptide of interest to be identified as the N-terminal 33 residue peptide in which the only tyrosine is Tyr 33. Thus H chain Tyr 33 was shown to be a contact amino acid residue in the site of McPC 603 protein. These results provide chemical evidence confirming previously reported x-ray crystallographic identification of H chain Tyr 33 in the site of McPC 603 protein.

Amino Acid Sequence

The expression on mouse lymphoid cells of Th-B, an antigen common to mouse B cells and thymus cells.

A new cell-surface antigen of mouse lymphocytes, which was found earlier on normal and malignant plasma cells and about half the normal thymus cell population, has been shown to be on mature B cells and on the least immunocompetent subpopulation of cells of the thymus. The antigen was first detected by the cytotoxic effect on relevant cells of an in vivo purified rabbit antiserum raised against cells of the mouse IgM-producing plasma cell tumor MOPC-104E. We have now used a cell-transfer method to examine the effect of this antiserum (RantiM104E) on immunocompetent lymphocytes of spleen, including separated splenic B and T cells and thymus and bone marrow cells. We have found the antigen on the immunocompetent B lymphocytes of the spleen, but not on any other of the immunocompetent cells examined. The method involves determining the effect of the antiserum on the development of plaque-forming cells in the spleens of irradiated mice that have received lymphocytes from immune or non-immune donors by treating the lymphocyyes with RantiM104E antiserum before transfer. Plaque-forming cells are suppressed when antiserum-treated spleen cells are transferred to the irradiated mice.This suppression was found to be due to action on only the splenic B cells. The helper activity of splenic T cells was not reduced significantly by antiserum treatment. Neither was the helper activity of thymus cells similarly treated reduced by the antiserum. We found, in fact, that the subpopulation of the thymus cells which is resistant to the antiserum was more immunocompetent than the total thymus cell population. In addition, the hydrocortisone-resistant thymus cells were also found to be resistant to the cytotoxic action of the antiserum. The antiserum had no effect on bone marrow cells in the cell-transfer procedure. The antigen involved, which we are designating "Th-B" appears to be a B cell line marker which appears relatively early during the differentiation of mouse B cells from precursor cells and is lost during maturation of T cells.

Animals

An experimental model for evaluation of factors in tumor escape from immunological attack.

A model system is presented for studying the factors involved in tumor immunity. The initial observations with this system concern the importance of dose and route of administration of tumor cells on tumor growth. The data show that myeloma tumor cells, when inoculated i.v.in relatively large numbers, are eradicated by the immune response of an allogeneic host; tumor cells administered i.v. in smaller number escape from immune attack even though the host has the potential to mount an immune response. BALB/c mouse myeloma cells (MOPC-21) were transplanted s.c., i.p., or i.v. into H-2-compatible allogeneic DBA/ 2 mice. There was a marked difference in the response of the host to tumor given s.c. or i.p. as compared to tumor given i.v. Thus s.c. or i.p. inoculation resulted in lethal tumor growth when 5 x 10-3 or more tumor cells were given. In contrast, the outcome of i.v. inoculation depended on tumor cell dose. Although small cell doses ( 5x 10-4 down to 10-2) resulted in lethal tumor gosulted in lethal tumor growth with only 10% survival, large cell doses (10-5 to 5 x 10-7) resulted in tumor rejection and 70% survival. DBA/2 mice possess the immunological ability to react agaist the tumor when large doses of tumor cells (10-7) are given i.v. or i.p., since spleen cells obtained from such mice were found to be able to suppress the growth of MOPC-21 when a mixture of spleen cells and tumor cells was inoculated. On the basis of these initial observations, our model appears to relate especially to the idea that, in autochithonous tumor development or in metastasis of tumor, a small number of antigenic tumor cells, perhaps even a single cell, usually grows into a frank tumor in spite of the immunological competence od the host to respond to the tumor cells.

Animals