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Biomedical subjects

N Hollander

Publications and source records attributed to N Hollander.

At least 37 records · Page 2Linked to original sources
PubMed1986

A synergistic effect between anti-idiotype antibodies and anti-neoplastic drugs in the therapy of a murine B-cell tumor.

Antibodies directed against idiotypic determinants of the cell-surface IgM of a B lymphoma, 38c, were effective in delaying development of the tumor and in some instances in preventing its growth. The efficacity of the anti-idiotype antibodies was markedly increased when they were injected in combination with anti-neoplastic drugs. Since chemotherapy, as such, is limited by the general toxicity of the drugs it was of advantage to apply them in low doses. The drug doses used were mostly ineffective by themselves, yet were active in combination with the antibody in a more than additive fashion. We performed studies designed to elucidate the mechanism of the synergy between the anti-idiotype antibodies and the drugs. The data suggest that the activity of the antibody is partly indirect and is mediated through the host's effector cells. In the case of one drug, daunomycin, the activity is also, at least in part, mediated through peritoneal exudate cells (PEC). Daunomycin injected intraperitoneally activated PEC. Such activated PEC, when injected into recipient mice, could replace the drug in its synergy with the antibody. In conclusion, it was shown that it is possible to increase the effectiveness either of antibodies to tumor cells or of cytotoxic drugs by combination therapy.

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PubMed1985

The immunotherapeutic effect of anti Lyt-1 antibodies on local and metastatic tumor growth.

Monoclonal antibodies against the T cell differentiation antigen Lyt-1 were effective in the therapy of the murine Lewis lung carcinoma (3LL). A possible mechanism whereby anti Lyt-1 antibodies directly effect the tumor cells was unlikely because 3LL cells lack the Lyt-1 antigen. In addition, the curative effect of anti Lyt-1 antibodies was abrogated in mice depleted of T cells, supporting a mechanism whereby host Lyt-1+ cells were involved in tumor therapy. Treatment with anti Lyt-1 antibodies was not accompanied by depletion of Lyt-1+ cells from lymphoid organs, indicating that the administered antibodies altered Lyt-1+ cell functions without effecting their frequency. In view of the in vitro enhancing effects of anti Lyt-1 antibodies on responses, it is suggested that the potentiation of Lyt-1+ cell activity by passively administered anti Lyt-1 antibodies results in tumor rejection.

Animals↗
PubMed1985

The functional association of Lyt antigens with lymphokine production.

The effects of anti-Lyt antibodies on secretion of lymphotoxin, macrophage-activating factor and interferon were studied. Anti-Lyt-1 antibodies added to primary mixed lymphocyte reactions (MLR) significantly enhanced lymphokine secretion, whereas anti-Lyt-2 antibodies had no effect in primary responses. However, when added to secondary MLR, anti-Lyt-1 antibodies manifested moderate enhancing effect on lymphokine levels, whereas anti-Lyt-2 antibodies markedly reduced lymphokine secretion. These results suggested that T cells of different subsets produced lymphokines during primary and secondary responses. The Lyt phenotype of T cells involved in lymphokine secretion and the effects of anti-Lyt antibodies on selected T-cell subsets were therefore studied. It was demonstrated that the majority of lymphokine producing cells during primary MLR reside within the Lyt-1+2- population, which was potentiated by anti-Lyt-1 antibodies, but unaffected by anti-Lyt-2 antibodies. However, during secondary MLR, a considerable proportion of lymphokines was produced by the Lyt-1-2+ population, which was blocked by anti-Lyt-2 antibodies. Lymphokine production induced by concanavalin A, in contrast to that induced by alloantigens, was unaffected by anti-Lyt-2 antibodies. The implication of these results on the role of Lyt molecules in T-cell functions is discussed.

Animals↗
PubMed1985

Lyt-2+ suppressor T cells are resistant to anti-Lyt-2 antibody blocking.

Lyt-2 molecules play a role in antigen recognition by cytotoxic T lymphocytes (CTL). In an attempt to determine whether Lyt-2 molecules play a similar role in suppressor T cell (Ts) functions, the effect of anti-Lyt-2 antibodies on Ts generation and effector activity was studied. Allospecific Ts were induced in allogeneic mixed lymphocyte cultures (MLC). Anti-Lyt-2 antibodies added to MLC in the absence of complement abolished CTL generation, but had no effect on concomitant induction of Ts. In a different experimental system, allospecific Ts were induced in cultures treated with pyrilamine, which blocks generation of CTL but allows differentiation of Ts. The addition of anti-Lyt-2 antibodies to pyrilamine-treated MLC resulted in unaffected induction of Ts. It was further demonstrated that the effector activity of Ts was as resistant to anti-Lyt-2 antibodies as their induction, in contrast to the cytolytic activity of CTL, which was inhibited by the same antibodies. Ts in the present experimental system were Lyt-2+ antigen-specific cells. It therefore appears that Lyt-2 molecules, although expressed on both CTL and Ts, are involved in CTL activity, but do not play an essential role in Ts function.

Animals↗
PubMed1985

Antibodies to nonpolymorphic determinants of the Thy-1 molecule inhibit T cell proliferation.

The effect of anti-Thy-1 monoclonal antibodies on murine mixed lymphocyte reactions and concanavalin A-induced mitogenesis were investigated. It is demonstrated that rat antibodies against nonpolymorphic determinants of the murine Thy-1 antigen inhibited cell proliferation in the absence of complement. In contrast, antibodies against polymorphic determinants of Thy-1 had no effect on T cell activation. Inhibition of T cell proliferation did not depend on the isotype of the blocking antibody, because both IgM and IgG antibodies against monomorphic determinants were inhibitory, whereas IgM or IgG antibodies against allotypic determinants were inactive. In addition, the blocking activity could not be attributed to the xenogeneic (rat) origin of the antibodies to nonpolymorphic Thy-1 determinants, because rat anti-Thy-1.2 antibodies had no effect on cell activation. Thus, the efficacy of anti-Thy-1 antibodies as T cell inhibitors was determined by the antibody specificity. The suppressive mechanism of anti-Thy-1 antibodies was effective throughout the entire course of mixed lymphocyte reactions. Addition of antibodies at any time point during the first 90 hr of a 120-hr mixed lymphocyte culture resulted in significant suppression of the proliferative response. However, in some cases an early enhancement preceded suppression of the response. The modulation of proliferative responses by anti-Thy-1 did not result from a nonspecific mitogenic effect of the antibodies on T lymphocytes, because no effects were observed when antibodies were added to responder cells alone. These results suggest that the Thy-1 molecule, or a molecule that is located on the cell membrane in close proximity to the Thy-1 antigen, is involved in the activation of T lymphocytes.

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PubMed1984

The differential expression of H-2K versus H-2D antigens, distinguishing high-metastatic from low-metastatic clones, is correlated with the immunogenic properties of the tumor cells.

Two clones of the 3LL Lewis lung carcinoma, a low-metastatic clone A9 and a high-metastatic clone D122, were studied for MHC expression and immunogenic properties. Using monoclonal antibodies, we demonstrated that the A9 clone expresses both the H-2Kb and the H-2Db, whereas the D122 expresses only the H-2Db, and lacks the expression of the H-2Kb encoded molecules. Cells of the low-metastatic clone A9 grew progressively in syngeneic (C57BL/6J) or in F1 mice, but were rejected in allogeneic recipients. The high-metastatic D122 grew progressively in all mouse strains tested, yet metastases were formed only in syngeneic recipients. When H-2 recombinant mice were used, the A9 again manifested a significantly greater immunogenic potency than the metastatic D122, which grew in all 4 recombinants tested. Metastases, however, were formed in B10HTG and to a lesser extent in B10A(4R), thus indicating that metastasis formation is restricted by both C57BL background and H-2Db sub region. We subsequently tested whether the higher immunogenicity of the H-2Kb-positive A9 cells is expressed also in syngeneic mice, to examine whether this could account for its low metastatic phenotype. We found that immunization by A9 cells significantly inhibited the growth of a subsequent A9 graft and even of D122, yet D122 did not retard the growth of secondary D122 or A9 cells. The increased immunogenic effect was expressed also in the generation of syngeneic cytotoxic lymphocytes by A9 but not by D122 cells. We suggest that expression of H-2K molecules on the 3LL clones, immunogenicity and the metastatic phenotype are causally related in this system.

Animals↗
PubMed1984

Immunotherapy of lymphoid and nonlymphoid tumors with monoclonal anti-Lyt-1 antibodies.

Monoclonal antibodies against the T cell differentiation antigen Lyt-1 were effective in the therapy of transplanted mouse tumors. A possible mechanism whereby anti-Lyt-1 antibodies directly bind and affect the tumor cells was excluded by the following findings: a) growth of lymphoid and nonlymphoid tumors (which lack Lyt-1 antigen) was affected by anti-Lyt-1 antibodies; and b) the curative effect of passively administered anti-Lyt-1 anti-bodies was abrogated in mice depleted of T cells, supporting a mechanism whereby host Lyt-1+ cells were involved in tumor therapy. Treatment with anti-Lyt-1 antibodies was not accompanied by depletion of Lyt-1+ cells from lymphoid organs, indicating that the administered antibodies altered Lyt-1+ cell functions without affecting their frequency. In view of the in vitro enhancing effects of anti-Lyt-1 antibodies on a variety of immune responses (including lymphokine secretion and generation of cytotoxic T cell), it is suggested that the potentiation of Lyt-1+ cell activity by passively administered anti-Lyt-1 antibodies results in tumor rejection.

Animals↗
PubMed1981

Effects of Lyt antibodies on T-cell functions: augmentation by anti-Lyt-1 as opposed to inhibition by anti-Lyt-2.

Monoclonal anti-Lyt-1 (alpha Lyt-1) and alpha Lyt-2 manifest inverse effects on allogeneic mixed lymphocyte reactions when added to the reaction mixtures without complement. alpha Lyt-1 augments cell proliferation and generation of cytotoxic cells but has no effect on cell-mediated cytolysis, whereas alpha Lyt-2 blocks cell proliferation, generation of killer cells, and cytolytic activity of killer cells. The augmenting effect of alpha Lyt-1 cannot be attributed to a direct mitogenic effect on T cells. Both inhibition by alpha Lyt-2 and potentiated by alpha Lyt-1 require interaction of responder cells with the antibodies during the first 24 hr of the mixed lymphocyte reaction, indicating that early stages of the reaction are sensitive to Lyt antibodies. The enhancing effect of alpha Lyt-1 on alloantigen-induced T-cell proliferation is associated with augmented production of T-cell growth factors. When alpha Lyt-1 is present in mixed lymphocyte cultures, the supernatant media collected after 24 or 48 hr of culture induce higher proliferation of activated T cells compared to media of mixed lymphocyte cultures incubated in the absence of antibodies or in the presence of alpha Lyt-2 which has no effect on secretion of growth factors. The differences in the effects of alpha Lyt-1 and alpha Lyt-2 could not be attributed to differences in heavy chain constant region functions because both were of the same lambda 2A immunoglobulin class and were used at the same concentration. The data suggest a possible role for Lyt-1 molecules in early activation and mitogenesis processes such as production of growth factors.

Animals↗
PubMed1980

Blocking effect of lyt-2 antibodies on T cell functions.

Monoclonal anti-Lyt-2 antibodies blocked effector function of cytotoxic thymus-derived (T) cells in the absence of added complement. Cytolysis of both allogeneic cells and syngeneic lymphoma or sarcoma target cells was inhibited at the level of the effector lymphocytes. Anti-Lyt-1 and anti-Thy-1 antibodies did not block killer cells. Proliferation of T cells in mixed lymphocyte culture was also inhibited by anti-Lyt-2, but not affected by anti-Lyt-1 or anti-Thy-1 antibodies. Although Lyt-1+ lymphocytes were required in the mixed lymphocyte reaction as helper cells for proliferation of Lyt-2+ lymphocytes, their helper function was not affected by the presence of Lyt-1 antibodies. Thus, although anti-Lyt-1, anti-Lyt-2 and anti-Thy-1 were of the same gamma 2A immunoglobulin class, had high titers, and interacted with T cells to the same extent, only anti-Lyt-2 blocked T cell functions. Polyclonal activation of T lymphocytes by concanavalin A, in contrast to activation by alloantigens, was not inhibited by Lyt-2 antibodies, suggesting that Lyt-2 antibodies interfere with T cell function at the level of the T cell antigen-receptor. The role which Lyt-2 molecules may play in T cell function is discussed.

Animals↗
PubMed1979

An immunoregulatory factor associated with spleen cells from tumor-bearing animals. III. Characterization of the factor's target cells.

An immunoregulatory factor associated with spleen cells from tumor-bearing mice was found to potentiate the generation of antibody-producing cells (APC). In an attempt to characterize the target cell of this enhancing factor (EF), its activity in mice devoid of mature T lymphocytes was tested. Levels of anti-SRBC APC were augmented when EF was injected together with SRBC to nude mice and "B" mice. In addition, EF potentiated the antibody response against the IgM-inducing T-independent pneumococcal plysacchardide SIII antigen. These results suggest that EF most probably exerts its enhancing influence directly on B lymphocytes. In a different line of experiments adoptive secondary responses were performed. Mice were immunized with SRBC as carrier or with the NIP-chicken erythrocytes (as a source of NIP-specific primed B cells) in the presence or absence of EF. Various combinations of spleen cells from the donor immunized mice were transferred in a mixture with NIP-SRBC to lethally irradiated recipient mice, EF did not exert any potentiation effect on helper function, except when primed B cells were used. In contrast, a clear activation or clone expansion of hapten-specific B cells was observed. These findings indicate that the enhancing factor from tumor-bearing animals directly affected the antigenic triggering of B lymphocytes and their subsequent proliferation and differentiation to antibody-producing cells.

Animals↗
PubMed1979

Allogeneic cytolysis of reconstituted membrane vesicles.

The successful use of lipid bilayer model membranes as targets for cytotoxic lymphocytes is described. Lipid vesicles were made from a mixture of dipalmitoyl lecithin, dimyristoyl lecithin, and cholesterol. Membrane proteins of LSTRA or EL4 tumor cells (as source of H-2 antigens), human eye muscle membrane proteins (as supporting proteins), and 51Cr marker were inserted into the lipid vesicles. Incubation of the reconstituted vesicles with lymphocytes sensitized in mixed lymphocyte cultures against allogeneic cells resulted in the specific release of intravesicular 51Cr. Vesicle damage was mediated by thymus-derived lymphocytes. H-2 antigens could be incorporated into vesicles without eye muscle proteins. However, immune damage of the vesicles could not be demonstrated when vesicles inserted with H-2 antigens in the absence of eye muscle proteins were used as targets.

Animals↗
PubMed1979

Reimbursing hospice care: a Blue Cross and Blue Shield perspective.

The Associations' "Initial Statement on Hospice Care and Payment for Hospice Services" comprises three criteria and many recommendations. The statement can guide local Plans and other third party payers, wary of repeating past mistakes that increased costs without improving care.

Blue Cross Blue Shield Insurance Plans↗
PubMed1978

An immunoregulatory factor associated with spleen cells from tumor-bearing animals. I. Effect on tumor growth and antibody production.

An immunopotentiating factor associated with spleen cells of C57BL/6J mice bearing the 3LL tumor is described. Supernatants of cultured spleen cells from tumor-bearing mice (TBM) augmented the generation of both 19S and 7S antibody-producing cells, when injected with sheep erythrocytes into syngeneic C57BL/6J mice. The enhancing supernatant acted both as a polyclonal activator, when injected in the absence of antigen, and as a potentiator of specific antigen-dependent humoral immune responses, when injected in the presence of antigen. It was found to augment induction of specific memory, but not memory expression. Concomitantly with their influence on humoral immune responses, TBM spleen cell supernatants enhanced tumor growth when injected, mixed with 3LL tumor cells, into syngeneic recipients. The secretion of a factor which augments antibody production was not confined to the 3LL tumor system. Spleen supernatants of C47BL mice carrying the B16 melanoma and those of C3H mice carrying the KHT sarcoma had a similar effect on antibody production. These findings suggest that an immunoregulatory factor(s) appears in spleen cells of TBM as a result of their interaction with the neoplastic tissue. This factor can potentiate production of antibodies, possibly also against tumor-associated antigens. The relevance of the immunopotentiating effects of such factor(s) to tumor growth is discussed.

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