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L A Manson

Publications and source records attributed to L A Manson.

At least 19 recordsLinked to original sources
PubMed1994

Anti-tumor immune responses of the tumor-bearing host: the case for antibody-mediated immunologic enhancement.

Analyses of host immune responses taking place during the growth from small inocula either as ascites or as solid subcutaneous tumors of a number of carcinogen-induced, immunogenic, murine tumors have shown that host immune responses are fully compatible with progressive tumor growth in their syngeneic hosts. Both B cell (antibody) and T cell ("killer cell") responses were detected in situ, and progressive tumor growth continued in concert with these responses. Tumor cell, after 2 weeks of growth in vivo, became resistant to the induced killer cells. The modulating agent appears to be anti-tumor antibody. The kinetics of the appearance of the antibody response and its specificity suggested that the responsible epitopes are uniquely expressed on tumor cells (oncotopes). Anti-oncotope antibody was found bound to these resistant tumor cells, yet the cells were fully capable of growing progressively, despite the presence of killer cells in their midst. These observations are compatible with data first reported 35 years ago suggesting that anti-tumor antibody promoted or enhanced tumor growth. Immunized mice have T-cytotoxic cells (CTL, MHC-restricted) in their spleens and lymph nodes, whereas the killer cells found in the ascites of tumor bearers were MHC-unrestricted. In vivo grown tumor cells were completely resistant to spleen CTL of immune mice. The implications of these observations are of consequence not only in the design of effective immunotherapeutic protocols to eliminate cancer but also for a better understanding of self-tolerance, autoimmunity, and the genetics of the cancer formation. A unifying hypothesis is presented which explains how antibody-mediated immunologic enhancement is operative both in permitting progressive tumor growth and in allograft retention.

Animals↗
PubMed1994

MedLine update.

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Animals↗
PubMed1991

Does antibody-dependent epitope masking permit progressive tumour growth in the face of cell-mediated cytotoxicity?

It is not clear how immunogenic tumours can grow from small inocula in syngeneic hosts that mount both T-cell and B-cell responses. In this article Lionel Manson argues that antibody coats the tumour cells, protecting them from attack by cytotoxic lymphocytes, and thus permits the tumour to continue to grow and overwhelm the host. These observations may explain the paradox that an immunogenic tumour overwhelms the tumour-bearing host in the face of an ongoing anti-tumour immune response.

Animals↗
PubMed1987

A subset of normal human B lymphocytes expresses an antigen cross-reactive with gp52 of murine mammary tumor virus.

Three monoclonal antibodies (MAbs), VE7, VIG3, and IXF9, that detect the 52-kd glycoprotein (gp52) of murine mammary tumor virus (MMTV) were tested for reactivity on normal human tonsillar lymphoid cells in an indirect immunofluorescence assay. Two of the MAbs, VE7 and VIG3, reacted with subpopulations of B cells, whereas the third MAb, IXF9, showed only very low-level reactivity with human lymphoid cells. VE7 and VIG3 also reacted with small populations of peripheral blood lymphocytes, and all three MAbs reacted with some transformed human cell lines. The data suggest that subpopulations of normal human lymphocytes express antigens that are cross-reactive with the MMTV gp52, although not all of the viral gp52 epitopes are expressed on the surface of these cells.

Antibodies, Monoclonal↗
PubMed1987

Novel tumor-specific antigen(s) response observed in a syngeneic lymphoma-bearing host.

Immunoglobin (Ig) has been found to accumulate on P815Y (H-2d) and L5178Y (H-2d) tumor cells during progressive growth in syngeneic host DBA/2 mice. Density of the accumulated Ig per cell increases as the tumor grows while the tumor cells become resistant to lysis by ascitic syngeneic cytotoxic cells. Tumor cells grown in vivo coated with this specific Ig no longer bind significant amounts of antibodies against H-2D and H-2K antigens. The membrane-bound Ig reacts with a rabbit antimouse Fab and a rabbit antimouse IgM reagent, but it does not react with a rabbit antimouse IgG or IgA reagent. It binds specifically to tumor cell lines that are sensitive to the ascitic cytotoxic cells but not to resistant tumor cell lines. The membrane-bound Ig can be eluted from tumor cells with 3 M NaSCN or 0.2 M acetic acid. Binding studies indicate that this eluted Ig is not an anti-H-2D/K antibody, yet it immunoprecipitates H-2D/K antigens from NP40 lysates of P815Y cells. It is proposed that the Ig is directed against a tumor antigen that is physically associated with the H-2D/K antigens of the tumors.

Animals↗
PubMed1983

Characterization of "H-2K,D-like structures" on MM2 x mouse L cell hybrids. II. An "H-2Kd-like" structure on C3H-derived tumor.

Anti-MM2 serum, which had been prepared by immunizing C3H/He mice with syngeneic MM2 mouse mammary ascites tumor, immunoprecipitated "H-2K,D-like" molecules on DBA/2 and C3H.H-2 degrees lymph node cells as well as on somatic cell hybrids between MM2 tumor and mouse L cells. Preclearing of lysates from C3H.H-2 degrees lymph node cells with anti-H-2.31 serum removed all "H-2K,D-like" molecules reactive with anti-MM2 serum, indicating that the molecules detected by anti-MM2 serum are H-2Kd antigens. The anti-H-2.31 serum detected an "H-2K,D-like structure" on the hybrid cells and absorption of the anti-H-2.31 serum with the hybrid cells deprived the serum of anti-H-2Kd reactivity. The hybrid cells could induce antibodies against the H-2Kd antigen in C3H/He mice. These results indicate that on the hybrid cells, whose parental cells were both derived from C3H mice, there is an "H-2K,D-like structure" that has the H-2Kd private specificity. Absorption of anti-MM2 serum with EL4 cells did not affect the capacity of the serum to detect the H-2Kd antigen on C3H.H-2 degrees lymph node cells, indicating that the "H-2Kd-like structure" is distinct from "H-2K,D-like structure A" which was previously reported. Nine isozymes were examined and MM2 cells, mouse L cells, and the hybrids were found to have the same isozyme markers as those of the C3H/He mouse.

Animals↗
PubMed1983

A viral coat glycoprotein (gp52MuMTV) has detergent-sensitive and detergent-resistant epitopes in the same molecule.

Two monoclonal antibodies (IIB5 and IC12) specific for the gp52 coat glycoprotein of mouse mammary tumor virus are directed against epitopes on the gp52 that are sensitive to a non-ionic detergent, Nonidet P-40. There are other epitopes on this molecule that are stable in the detergent, as seen in immunoprecipitation studies with other anti-gp52 monoclonal antibodies (VE7, IIIA1, IVC11).

Antibodies, Monoclonal↗
PubMed1983

An antigen cross-reactive with gp52 of mammary tumor virus is expressed on a B cell subpopulation of mice.

The reactivity of murine lymphoid tissue with biotinylated F(ab')2 fragments of monoclonal antibody VE7 (BIOT VE7), which reacts with gp52 of murine mammary tumor virus (MuMTV), was tested with fluoresceinated avidin in an indirect fluorescent antibody assay on live splenocytes. A small percentage of splenic lymphocytes in C3H/He mice infected exogenously with MuMTV, and in C57BL/6 mice that, like C3H/He, harbor several endogenous MuMTV proviruses in their genomes, were reactive with the monoclonal antibody. The antigen-positive splenocytes were shown to represent a subpopulation of B cells. The possible nature of the B cell-associated antigen recognized by monoclonal antibody VE7 is discussed.

Animals↗
PubMed1981

Characterization of "H-2K,D-like structures" on MM2 X mouse L cell hybrids. I. "H-2K,D-like" alloantigen encoded by the D region and/or to the right of the D region of the H-2 gene complex.

It was found that anti-MM2 serum, which had been prepared by immunizing C3H/He mice with syngeneic MM2 mouse mammary ascites tumor, detected molecules of 44-46,000 and 12,000 daltons on EL4 leukemic cells and on C57BL/6 lymph node cells, as well as on somatic cell hybrids between the MM2 and mouse L cells. Experiments with a known rabbit anti-mouse beta2-microglobulin serum showed that the two molecules detected by anti-MM2 serum were hydrophobically associated with each other in membrane extracts; thus, the antigen detected by anti-MM2 serum was structurally similar to H-2K and D antigens. Preclearing of lysates from C57BL6 lymph node cells with a mixture of anti-H-22, anti-H-2.33, and anti-H-2.28 sera did not remove the "H-2-like" antigen, indicating that the antigen was distinct from the H-2Kb and Db molecules. Neither C3H/He nor B10.BR lymph node cells expressed the "H-2-like" antigen, but B10.A(4R) and B10.AM lymph node cells did possess the antigen. Absorption of anti-MM2 serum with EL4 cells abolished the capacity of the absorbed serum to precipitate the "H-2-like" antigen activity on C57BL/6 lymph node cell extracts and reduced the "H-2-like" radioactive peaks of the hybrid cells. These results indicate that there are at least two components being recognized by the anti-MM2 serum in hybrid cells between MM2 tumor and mouse L cells, both of which had originated in the C3H/He mouse (H-2k). One is the same as or cross-reactive with an "H-2-like" alloantigen of normal C57BL/6 lymph node cells (H-2d) and the other is another "H-2-like" antigen. Experiments with recombinant mice show that the "H-2-like" alloantigen on lymph node cells is coded for by the D region and/or to the right of the D region of the major histocompatibility complex (MHC).

Animals↗
PubMed1981

Monoclonal antibodies against antigens displayed on a progressively growing mammary tumor.

We have produced lymphocyte hybridomas between mouse myeloma cells and either spleen cells of C3H/f/C57BL/6 mice bearing the Mm5mt/c1 tumor-producing murine mammary tumor virus (MMTV) or spleen cells from Fisher rats inoculated with the same tumor. Two classes of hybridoma-secreted monoclonal antibodies were obtained. In the first class are IVC11, IIIA1, and VE7, each of which precipitated a 52,000-dalton protein from 125I-labeled purified preparations of MMTV and [3H]glucosamine-labeled Mm5mt/c1 cell extracts. A second class of monoclonal antibodies, represented by IC12 and IIIB5, reacted specifically with C3H MMTV-secreting cells in radioimmunoassays (RIA) with whole cells and did not precipitate proteins with labeled virus or metabolically labeled Mm5mt/c cell extracts. IC12 and IIB5 could be distinguished from each other in a RIA in which antigen discs were prepared from a membrane preparation of Mm5mt/c1 cells. In this assay, IC12 antibody was blocked from reacting with discs precoated with goat anti-MMTV, and IIB5 antibody was not.

Animals↗
PubMed1979

Immunological analysis of A strain mice bearing the A-10 mammary adenocarcinoma.

The present investigation was undertaken to determine whether antitumor antibodies are produced by A strain mice during the growth of a transplantable mammary adenocarcinoma (A-10). The antibody response was monitored by a sensitive radioimmunoassay which can detect 1 ng of antibody. No evidence of a humoral antitumor response was observed in animals given i.p. or s.c. injections of A-10 ascites cells. Control experiments showed that a humoral response was detectable 1 week after the inoculation of an allogeneic tumor. Immunoglobulin binds nonspecifically to cells via an Fc portion of the immunoglobulin molecule, and this was seen with a tumor bearer serum pool and with immunoglobulin preparations eluted from A-10 ascites cells. No specific antitumor antibody was found in these sources. The A strain mice could not be immunized to reject a challenge of live A-10 cells with mitomycin C-treated A-10 cells, with neuraminidase-treated A-10 cells, or with A-10 membrane preparations. It was concluded that the A-10 tumor is not immunogenic in its host of origin.

Adenocarcinoma↗