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Biomedical subjects

S Raychaudhuri

Publications and source records attributed to S Raychaudhuri.

At least 55 records · Page 3Linked to original sources
PubMed1989

Characterization of "regulatory" idiotope-specific T cell clones to a monoclonal anti-idiotypic antibody mimicking a tumor-associated antigen (TAA).

As reported previously, 3A4 is a paratope-specific anti-idiotypic mAb and induces cellular and humoral anti-tumor-associated Ag (TAA) responses. In this study, the specificity, MHC restriction and Ag processing requirement of Th cell lines and clones were determined that recognize an idiotypic determinant (Id) on 3A4. The anti-Id-3A4 is part of a tumor-associated idiotypic network which is involved in the regulation of the immunity against the DBA/2 L1210/GZL tumor. These 3A4-Id-specific T cell clones are phenotypically Th cells and recognize Id in the context of MHC class II molecules under MHC restriction. Moreover, the recognition of Id by these T cell clones is chloroquine sensitive, suggesting that they recognize processed Id. However, the 3A4-Id-specific T cell clones respond only to 3A4 and not to TAA. Because these clones do not recognize TAA, their biologic role in antitumor immunity could be as regulatory T cells involved in the idiotypic network regulation.

Animals↗
PubMed1989

Revised immune network concepts.

The idiotype network concept needs to be revised in order to be in agreement with current data on protein/protein interactions, with the phenomenon of T and B cell recognition of idiotopes, and with the failure of certain anti-idiotypes to stimulate a given immune response. It is proposed that the distinction among Ab2 alpha, beta, and gamma is abandoned, as well as the concept of an internal image idiotope which mimics the three-dimensional shape of nominal antigen. In place of these definitions, the concept of "network antigen" is introduced. Network antigens are potentially the entire repertoire of anti-idiotypes. However, their biological effectiveness is controlled and established by two factors: (i) the affinity to the idiotype Ig receptor; and (ii) the preexisting regulatory network segment that controls the outcome of immune stimulation or suppression. Screening for effective idiotype therapeutic agents has to be done with panels of anti-idiotype and idiotype antibodies in order to establish correlations between idiotope expression and disease progression. Recognizing the importance of network segments will be the first step in the direction toward a rational design of idiotype-based therapies.

Humans↗
PubMed1989

Potential role of anti-idiotype antibodies in active tumor immunotherapy.

The tumor-specified cellular and humoral immunity induced by anti-idiotype antibodies (Ab2s) 2F10 and 3A4 has been studied. Ab2s were made against a monoclonal anti-L1210/GZL lymphoma, 11C1. They were screened for their ability to block 11C1 binding to tumor, induce tumor-specific DTH and CTL responses, and induce an anti-tumor humoral response. Two Ab2s, 2F10 and 3A4, which were found to have similar fine specificity and to induce similar cellular and humoral responses, were compared for their ability to elicit tumor-protective immunity. Interestingly, only preimmunization with the 2F10 Ab2 protected animals from live tumor challenge. The possible causes for this discriminatory biological effect induced by otherwise similar Ab2s are discussed.

Animals↗
PubMed1989

Anti-idiotype antibodies: an alternative approach to tumor immunotherapy.

Studies presented in this paper examined the tumor-specific cellular and humoral immunity induced by anti-idiotype antibodies (Ab2s) 2F10 and 3A4. A panel of Ab2s was made against a monoclonal anti-L1210/GZL lymphoma, 11C1. The Ab2s were screened for their ability to block 11C1 binding to tumor, to induce tumor-specific DTH and CTL responses and to induce an anti-tumor humoral response. Two Ab2s, 2F10 and 3A4, were found to have similar fine specificity and to induce similar cellular and humoral responses. These were then examined for their ability to elicit tumor-protective immunity. Only preimmunization with 2F10 Ab2 protected animals from live tumor challenge, and in this paper the possible causes of this difference in otherwise similar Ab2s is discussed.

Animals↗
PubMed1987

Analysis of the idiotypic network in tumor immunity.

Herein we have analyzed the expression of idiotopes associated with a monoclonal anti-tumor-associated antigen (TAA) antibody in DBA/2 mice which have progressively growing tumors or resist tumor growth. A panel of eight monoclonal antiidiotypic antibodies raised against a monoclonal antibody which reacts with a mouse mammary tumor virus cross-reactive qp52 envelope protein (TAA) of the L1210/GZL lymphoma was used to measure the expression of idiotopes in sera from different treatment groups. Significant correlations between the expression of certain idiotopes and the growth of the tumor or the establishment of anti-tumor immunity are seen. 1) Idiotypes detected by anti-idiotype D11 are high in anti-idiotype immunized progressor or tumor-susceptible mice and low or absent in regressor mice, i.e., the mice immunized with the protective 2F10 anti-idiotype; 2) the 3A4-detected idiotypes are less frequent or absent in irradiated tumor-immunized regressor mice than in untreated mice challenged with live tumor or progressor mice; 3) no difference in the anti-TAA titers is seen in mice in which the tumor growth is inhibited and in mice in which the tumor grows; 4) no difference in 11C1 idiotype + anti-TAA titer was observed between regressor and progressor mice; and 5) mice with normal or accelerated tumor growth have higher titers of idiotypes detected by a polyclonal anti-idiotype. These findings provide evidence for a regulatory idiotype network induced by the growing L1210/GZL tumor or by anti-idiotypic immunization. The titer of anti-TAA antibody does not correlate with the biology of tumor growth, but certain idiotopes correlate with either progressive or regressive tumor behavior. Therefore, the target of the idiotype regulation is likely to be anti-tumor T effector cells. Effective idiotype therapy of tumors must deal with the complexity of idiotype regulation induced by the tumor itself and is unlikely to be successful if anti-idiotypes are used only as internal mimicry of a TAA.

Animals↗
PubMed1987

Tumor-specific idiotype vaccines. III. Induction of T helper cells by anti-idiotype and tumor cells.

In a previous report, we have demonstrated the induction of tumor-specific immunity by monoclonal anti-idiotype antibodies generated against a monoclonal anti-tumor antibody, 11C1, that also cross-reacts with mouse mammary tumor virus envelope glycoprotein gp52. Also, we showed that whereas one anti-idiotype antibody, 2F10, could induce protective immunity, another anti-idiotype antibody, 3A4, induced nonprotective immunity. Here we demonstrated the existence of T helper cells which recognize anti-idiotypes that exert differential controls on tumor growth. The qualitative nature of idiotype recognizing T cells generated in response to 2F10, 3A4, irradiated tumor, and progressively growing tumor was compared. The reactivity pattern of idiotype recognizing T cells obtained from 2F10 and irradiated tumor immunized mice were similar in nature in the sense that Lyt-2- T cells obtained from these immunized mice responded to both 2F10 and 3A4 as antigen, although T cells from tumor immunized mice responded better to 3A4 antigen. On the other hand, the idiotype-recognizing T cells obtained from 3A4-immunized mice showed a similar reactivity pattern to T cells isolated from mice during the early phase of tumor growth (within day 4 to 5 after the inoculation of 10(4) live tumor cells). Lyt-2- T cells isolated from mice immunized with 3A4 or during the early phase of tumor growth responded only to 3A4 antigen. The inability of Lyt-2- T cells, isolated from 4- to 5-day-old tumor in mice, to cooperate with 2F10-TNP is not due to the absence of 2F10 idiotype recognizing T cells as 2F10 id recognizing T cells are present when examined at the precursor level. These data on the idiotype specificity of T helper cells show a correlation with the presence of anti-tumor immunity. This information will help in the design and application of idiotype vaccine in tumor immunotherapy.

Animals↗
PubMed1987

Tumor-specific idiotype vaccines. II. Analysis of the tumor-related network response induced by the tumor and by internal image antigens (Ab2 beta).

In this study the tumor-specific immuneresponse induced by irradiated tumor cells (L1210/GZL) and by anti-idiotype antibodies was analyzed. The anti-idiotype antibodies (Ab2) were made against the paratope of a monoclonal antitumor antibody (11C1) that recognizes a tumor-associated antigen which cross-reacts with the mouse mammary tumor virus-encoded envelope glycoprotein 52. Two Ab2, 2F10 and 3A4, induced idiotypes expressed by the monoclonal antitumor antibodies 11C1 and 2B2. Cytotoxic T cells, generated by immunization with irradiated tumor cells, lyse 2F10 and 3A4 hybridoma cells. Furthermore, immunization with Ab2 induces tumor-specific cytotoxic T lymphocytes. The frequency of tumor-reactive cytotoxic T lymphocyte was found to be similar in mice immunized with Ab2 or irradiated tumor cells when examined at the precursor level. However, only 2F10 induces protective immunity against the growth of L1210/GZL tumor cells. The depletion of a L3T4+ T cell population from 2F10 immune mice was found to increase the effectiveness of transferred T cells to induce inhibition of tumor growth. The inability of 3A4 to induce antitumor immunity could be correlated with the presence of a population of Lyt2+ regulatory T cells. Collectively, these results demonstrate the existence of a regulatory network controlling the expression of effective tumor immunity. Our results demonstrate that selection of binding site-related Ab2 may not be a sufficient criteria for the development of an idiotype vaccine. A better understanding of the regulatory interactions induced by anti-idiotypes is needed for the design of effective antitumor immunotherapy.

Animals↗
PubMed1986

Tumor-specific idiotype vaccines. I. Generation and characterization of internal image tumor antigen.

The concept of idiotype vaccines against tumor-associated antigens (TAA) was tested in the DBA/2 L1210 lymphoma subline, L1210/GZL. Monoclonal antibodies against a TAA that cross-reacts with the envelope glycoprotein gp52 of the mammary tumor virus were used to make hybridoma anti-idiotype antibodies (Ab2). In this report we describe the characterization of monoclonal anti-idiotypic antibodies against the combining site of 11C1 (Ab1), which recognizes a shared determinant of gp52 of mouse mammary tumor virus (MMTV) and the TAA of L1210/GZL. Hybridomas expressing the internal image of gp52 were screened by an idiotype inhibition assay. Mice sensitized with radiated L1210/GZL cells produced specific delayed type hypersensitivity (DTH) against the Ab2 hybridoma. Five Ab2 hybridomas were selected and were used to immunize DBA/2 mice. Such immunized animals showed specific DTH reaction against a challenge with the L1210/GZL tumor cells. Similar results were obtained in mice immunized with purified Ab2. Fluorescence-activated cell sorter analysis demonstrated that fluorescence staining of L1210/GZL cells by 11C1 can be completely inhibited with preabsorption on Ab2 hybridoma cells. Mice immunized with 2F10 and 3A4 coupled to keyhole limpet hemocyanin (KLH) contained antibodies binding to MMTV. But only in mice immunized with 2F10-KLH was significant inhibition of L1210/GZL tumor growth observed. Collectively, these results indicate that certain anti-idiotypic antibodies can mimic the MMTV gp52 antigen, as well as the gp52-like epitope expressed on the L1210/GZL tumor cells. These properties of anti-idiotypic antibodies mimicking TAA could be exploited for making idiotype vaccines against tumors.

Animals↗
PubMed1986

Rational design and application of idiotope vaccines.

Current emphasis on risk factors associated with established vaccines and pressing needs for vaccines against certain viral transmitted diseases have stimulated the search for new conceptual and practical approaches to vaccine production. Among these developments, the idiotope vaccine method has produced promising results. In this review the basic and conceptual principles for idiotype vaccine design are discussed. A novel approach for identifying idiotopic structures in the three dimensional structure of internal idiotope antigens is developed. The method is based on the relationship of the immune response with the evolutionary variation and diversity of the immunoglobulin family. Idiotopic structures are found in specialized topographic regions on the surface of the immunoglobulin molecule. The knowledge of these idiotope domains will facilitate the synthesis of idiotope expressing peptides and the computer modeling of the three dimensional structure of internal idiotope antigens. Finally, the existing evidence for successful application of the idiotope vaccine method is summarized and new disease groups are identified which could benefit from the development of idiotope vaccines.

Autoimmune Diseases↗
PubMed1985

Cellular basis for neonatally induced T-suppressor activity. Primary B cell maturation is blocked by suppressor-helper interactions restricted by loci on chromosome 12.

The cellular mechanism and genetic restriction of neonatally induced HA-specific suppressor T (Ts) cells have been examined. The in vivo effect of these Ts cells on antibody production, primary B cell proliferation, B cell surface marker changes, and helper T (Th) cell priming during primary responses to HA have been determined. The results indicate that, although antigen-induced B cell proliferative responses and surface marker changes occur in the presence of Ts cells, differentiation to Ig secretion, and long-lived memory B cell production are prevented. Further, antigen-specific Th cell priming is completely ablated by Ts cells, suggesting that Ts act by preventing the delivery of Th signals required for both the later stages of primary B cell maturation, and the formation of memory B cell populations. Finally, in vivo cell mixing experiments using congenic mice indicate that this Ts-Th interaction is restricted by loci on mouse chromosome 12.

Animals↗
PubMed1984

Effect of frequency of plasma adsorption over protein A-containing Staphylococcus aureus on regression of rat mammary adenocarcinomas: modification of antitumor immune response and tumor histopathology.

Adsorption of the plasma of Sprague-Dawley rats having 7, 12-dimethylbenzanthracene (DMBA)-induced primary mammary adenocarcinomas with protein A-containing Staphylococcus aureus Cowan I (SAC) and reinfusion of the adsorbed plasma caused significant (p less than 0.05) regression of mammary adenocarcinomas. Adsorption of plasma was done at different intervals--weekly, biweekly, and on alternate days. Of these protocols, alternate-day adsorptions induced very fast (within a week) tumor regression (p less than 0.001). Other protocols also produced tumor regression; however, the effect was delayed. In long-term studies, the responding animals showed fewer tumor nodules than did the untreated controls. The plasma of the treated animals showed (a) a reduction in blocking activity, (b) an increase in antibody- and complement-mediated cytotoxicity, and (c) potentiation of the cytotoxic activity of peripheral blood mononuclear cells (PBMCs). Histopathological analyses of biopsied sections of tumors from treated animals showed (a) disruption of tumor cell architecture, (b) loss of glandular structure, (c) shrinkage of epithelial cells, and (d) moderate mononuclear cell infiltration. Thus, adsorption of the plasma of DMBA tumor-bearing rats with SAC allows an indigenous immune mechanism to function against autochthonous tumors to control their growth and cause regression.

Adenocarcinoma↗
PubMed1983

Restricted adult clonal profiles induced by neonatal immunization. Influence of suppressor T cells.

The effects of neonatal antigen exposure on the adult B cell repertoire have been examined by characterizing the influenza hemagglutinin (HA)-specific response of adult BALB/c mice given antigen soon after birth. Ligand exposure during early life exerts a profound and lasting effect upon the B cell repertoire, characterized by the expansion and preservation of particular antigen-reactive clones and the apparent loss of others. The precise subset of clonotypes selectively preserved depends upon the age at which antigen is first encountered; and is predictable given a knowledge of the emerging primary pool's dynamics and composition. The preserved (secondary) B cells differ from their unprimed precursors with respect to (a) expression of the surface marker detected by the monoclonal antibody J11d, and (b) susceptibility to T cell-mediated suppression. These studies thus demonstrate a strong relationship between the heritable dynamics of the emerging primary B cell repertoire and the effect of ligand-driven events upon repertoire phenotype. In addition, they provide a mechanistic model for certain forms of antigen-induced oligoclonal dominance, especially the phenomenon of original antigenic sin.

Aging↗
PubMed1982

Mechanism of regression of mammary adenocarcinomas in rats following plasma adsorption over protein A-containing Staphylococcus aureus.

The plasma from 7,12-dimethylbenz(a)anthracene-induced mammary tumor-bearing rats was adsorbed ex vivo with nonviable protein A-containing Staphylococcus aureus Cowan I and then injected into the rats, along with its original blood cells. Tumors in the treated rats showed significant (p less than 0.005) growth inhibition. There were fewer metastatic nodules; cellular cytotoxicity in the presence of plasma was augmented, and there was increased antitumor cytotoxic antibody activity in treated rats. Plasma from sham-treated rats, however, showed blocking activity. It appears that plasma perfusion over S. aureus decreases blocking activity and augments antitumor immunoreactivity of plasma. The exact mechanism by which growth of 7,12-dimethylbenz(a)anthracene-induced mammary tumors was inhibited in these treated Sprague-Dawley rats is not known. However, it is hypothesized that the observed tumor regression is at least partly attributable to the augmentation of antitumor immunoreactivity in the treated animals.

Adenocarcinoma↗
PubMed1982

Differential binding affinity of immobilized Concanavalin A-Sepharose 4B for normal and myelomatous immunoglobulins.

Immobilized Concanavalin A-Sepharose 4B (CSB) binds myeloma immunoglobulins (IgG through IgE) in larger proportions than it binds normal immunoglobulins. Some possible explanations for this are discussed. Also, CSB shows differential affinity among immunoglobulins, normal or myelomatous; its greatest affinity is for IgM and IgE. This property can be used to separate a large percentage of the IgM and IgE from both normal and myelomatous sera.

Humans↗
PubMed1981

Low-dose cyclophosphamide inhibition of transplantable fibrosarcoma growth by augmentation of the host immune response.

Preinjection of a low dose of cyclophosphamide (Cy) (500 microgram/mouse) either delayed or inhibited tumor appearance following the inoculation of transplantable 3-methylcholanthrene-induced fibrosarcomas in inbred male C3H/HeJ mice. This dose of Cy decreased the spleen weight by 13% and the total spleen cell count by 23%. However, the same dose could potentiate the footpad swelling reaction (FPSR) measured against Staphylococcus aureus antigen. Splenic lymphocytes from Cy-treated animals showed increased blastogenic response against phytohemagglutinin-M and bacterial lipopolysaccharide. Thus 500 micrograms Cy/animal may have depleted suppressor cell populations leading to: a) an increase in FPSR, b) increased blastogenic transformation of lymphocytes, and c) tumor growth inhibition.

Animals↗