Biomedical subjects

A Eisenthal

Publications and source records attributed to A Eisenthal.

At least 37 records · Page 2Linked to original sources

PubMed1993

Effect of allogeneic tumor cells, interleukin-2 and interleukin-6, on the growth of subcutaneous syngeneic tumors.

In the present study we demonstrate the ability of allogeneic M3 tumor cells to induce an antitumor response against the syngeneic tumor, when injected locally together with syngeneic B16 melanoma cells. The replacement of the allogeneic tumor cells with either syngeneic or allogeneic splenocytes had no effect on the growth of the syngeneic tumor. Systemic administration of both interleukin-2 (IL-2) and IL-6 did not affect the antitumor response induced by allogeneic tumor cells. When mice, previously injected with B16 and M3 cells, were rechallenged subcutaneously with B16 tumor cells at a different anatomical site, an inhibitory effect in some, but not all, experiments was observed. Systemic injections of either IL-2 or IL-6 did not alter the antitumor effects of the allogeneic and syngeneic tumor-cell mixtures. The significance of our results in developing immunotherapy modalities based on active immunization with allogeneic tumor cells and selected cytokines is discussed.

Animals↗

PubMed1993

Phenotypic and functional profile of peripheral blood mononuclear cells isolated from melanoma patients undergoing combined immunotherapy and chemotherapy.

In the present study we tested the phenotypic profile as well as several immunological responses of peripheral blood mononuclear cells (PBMC) isolated from melanoma patients. These patients underwent chemotherapy with dacarbazine and carboplatin from day 1 to day 22, followed by immunotherapy of low-dose recombinant interleukin-2 and recombinant interferon alpha administered subcutaneously from day 36 to day 75. The PBMC from 14 patients were isolated on day 0 before chemotherapy, on day 36 after chemotherapy and on day 76 after immunotherapy. After chemotherapy, a decrease in CD16+ cells and increase in CD3+ and CD4+ cells correlated with a significant decrease in the generation of lymphokine-activated killer (LAK) activity. After immunotherapy, an increase in CD16+ cells correlated with an increase in the induction of LAK activity. A comparison between responding and non-responding patients revealed statistically significant differences in LAK activity of PBMC and response to concanavalin A following chemotherapy, and in the percentage of CD8+ cells following immunotherapy. Our results point toward the value of continuing such a study on a larger population of cancer patients in order to select the appropriate bioassays for monitoring and predicting the clinical responsiveness to combined therapies.

Adult↗

PubMed1993

Increased projection of MHC and tumor antigens in murine B16-BL6 melanoma induced by hydrostatic pressure and chemical crosslinking.

The B16-BL6 melanoma, like most spontaneously arising tumors, is poorly immunogenic and expresses low levels of major histocompatibility complex (MHC) antigens. Treatment of cells of this tumor in vitro by hydrostatic pressure in the presence of adenosine 2',3'-dialdehyde (oxAdo), a membrane-impermeant crosslinker, caused elevated projection of MHC and a specific tumor antigen as demonstrated by flow-cytometric analysis. Maximum projection of both the MHC and the tumor antigens could be reached by application of 1200 atm for 15 min in the presence of 20 mM oxAdo. It is not yet clear whether this passive increase in availability of antigens on the cell surface originated from a dormant pool of antigens in the plasma membrane or from pressure-induced fusion of antigen-rich intracellular organelles (e.g. the endoplasmic reticulum). The immunogenic properties of the antigen-enriched B16-BL6 cells are described in the following paper.

Animals↗

PubMed1993

Induction of cell-mediated immunity against B16-BL6 melanoma in mice vaccinated with cells modified by hydrostatic pressure and chemical crosslinking.

In the preceding paper we have demonstrated an increase in presentation of both major histocompatibility complex antigens (MHC) and a tumor-associated antigen of the weakly immunogenic B16 melanoma by a straight-forward technique. The method consists in modulating the tumor cell membrane by hydrostatic pressure and simultaneous chemical crosslinking of the cell-surface proteins. In B16-BL6 melanoma, the induced antigenic modulation was found to persist for over 48 h, which permitted the evaluation of the ability of modified B16-BL6 cells to induce immunity against unmodified B16-BL6 cells. In the present study, we have shown that a significant systemic immunity was induced only in mice that were immunized with modified B16-BL6 melanoma cells, whereas immunization with unmodified B16-BL6 cells had only a marginal effect when compared to the results in control sham-immunized mice. The induced immunity was specific since a single immunization affected the growth of B16-BL6 tumors but had no effect on MCA 106, an antigenically unrelated tumor. The addition of interleukin-2 to the immunization regimen had no effect on the antitumor responses induced by the modified B16-BL6 cells. The cell-mediated immunity conferred by immunization with treated B16-BL6 cells was confirmed in experiments in vitro where splenocytes from immunized mice could be sensitized to proliferate by the presence of B16-BL6 cells. In addition, the altered antigenicity of these melanoma cells appeared to correlate with their increased susceptibility to specific effectors. Thus, 51Cr-labeled B16-BL6 target cells, modified by pressure and crosslinking, in comparison to control labeled target cells, were lysed in much greater numbers by effectors such as lymphokine-activated killer cells and allogeneic cytotoxic lymphocytes (anti-H-2b), while such cells remained resistant to lysis by natural killer cells. Our findings indicate that the physical and chemical modifications of the tumor cells that are described here may be considered as a simple yet effective method for the preparation of tumor vaccines, which could be applied in tumor-bearing hosts.

Animals↗

PubMed1993

Antitumor effects of recombinant interleukin-6 expressed in eukaryotic cells.

In the present study we evaluate the antitumor efficacy of a glycosylated molecule of interleukin-6 (IL-6), which was cloned and expressed in Chinese hamster ovary cells. When tested with two syngeneic murine tumors, the MC38 adenocarcinoma and the MCA106 fibrosarcoma, recombinant IL-6 (rIL-6) significantly reduced the number of day-3 established MC38 lung metastases, but had no effect on MCA106 lung metastases. A similar effect of rIL-6 was seen on day-3 MC38 liver metastases. The antitumor activity mediated by rIL-6 was achieved at doses of the cytokine ranging from 6 micrograms to 150 micrograms/day. There was no correlation between the responsiveness to rIL-6 of these two tumors and their susceptibility, in vitro, to a direct cytostatic effect of the cytokine or the increase in the expression of major histocompatibility complex (MHC) antigens after exposure to rIL-6. However, a correlation was seen between the antitumor response to rIL-6 and the initial number of tumor cells expressing MHC antigens. The possible role of MHC antigens expressed on tumor cells, the generation of MHC-restricted cytotoxic cells and the responsiveness to IL-6 are discussed.

Animals↗

PubMed1990

Induction of antibody-dependent cellular cytotoxicity in vivo by IFN-alpha and its antitumor efficacy against established B16 melanoma liver metastases when combined with specific anti-B16 monoclonal antibody.

We have previously shown the ability of different cytokines to induce antibody-dependent cellular cytotoxicity (ADCC) in murine cells in vitro. In addition we found that the administration to mice of IL-2-induced cells which mediated ADCC and that these cells were phenotypically similar to the cells induced in vitro. In the present study we tested the ability of various cytokines, including IL-1, TNF, IFN-alpha, and IFN-gamma to induce ADCC in vivo. We found that both IFN-alpha and IFN-gamma induced ADCC in the livers and spleens of C3H/Hen-treated mice and that these cytokines together with TNF enhanced the IL-2-induced ADCC in vivo. In C57BL/6 mice which, as previously shown, exhibit relatively low ADCC activity, IFN-alpha and IFN-gamma increased the IL-2-induced ADCC only when 100,000 U of IL-2 were used for priming. The effect of IFN-alpha on ADCC was dose dependent and was optimal after the administration of 200,000 U of the cytokine given three times a day for 3 days. Similar to the cells induced in vivo by IL-2, the precursors of the cells mediating ADCC were asialo GM1+ whereas the effectors were mainly nonadherent, Thy-1+ cells. IFN-alpha-generated cells mediating ADCC in the liver and spleen and, when combined with IL-2, ADCC was induced in the thymus as well. This effect of IFN-alpha on the induction of ADCC was exploited in an immunotherapy model in which we found that IFN-alpha significantly enhanced the antibody-mediated antitumor effect on established B16 melanoma liver micrometastases. Furthermore, when IL-2 and IFN-alpha administration was combined with the administration of mAb, a significantly reduced number of established 6- to 8-day B16 melanoma liver macrometastases and prolonged survival of tumor-bearing mice were seen. These studies imply that the administration of appropriate cytokine combinations may be a useful adjunct to the administration of mAb for the treatment of cancer in humans.

Animals↗

PubMed1990

Indomethacin up-regulates the generation of lymphokine-activated killer-cell activity and antibody-dependent cellular cytotoxicity mediated by interleukin-2.

Prostaglandins can inhibit the generation of lymphokine-activated killer (LAK) cells by interleukin-2 (IL-2) whereas indomethacin augmented the induction of LAK cells by inhibiting prostaglandin synthesis. In the present study we demonstrate that prostaglandin E2 substantially inhibited the generation of both LAK and antibody-dependent cellular cytotoxicity (ADCC) activity by IL-2. In addition, indomethacin enhanced the induction of LAK activity and ADCC in splenocytes exposed to IL-2 in vitro. The effect of indomethacin was dose-dependent, reaching an optimal effect at 1 microM when 100-1000 units/ml IL-2 were employed. The effect of indomethacin on the generation of ADCC was seen in cells taken from both tumor-bearing mice and normal mice. ADCC induced by IL-2 was augmented by culturing cells from the spleen, liver and lungs, in the presence of indomethacin. ADCC induced in the presence of IL-2 and indomethacin was mediated by cells that were mainly plastic non-adherent cells and expressed the asialo-GM1 glycolipid. The potential of indomethacin in combined therapy with cytokines and specific anti-tumor monoclonal antibodies is discussed.

Animals↗

PubMed1990

Effect of recombinant human tumor necrosis factor alpha on the induction of antibody-dependent cellular cytotoxicity in the treatment of established B16 melanoma liver nodules.

Incubation of C3H/Hen thymocytes in the presence of recombinant human tumor necrosis factor alpha (TNF) and interleukin-2 (IL-2) augmented the generation of antibody-dependent cellular cytotoxicity (ADCC) when compared to cells cultured in TNF or IL-2 alone. This effect was optimal when 100-200 units/ml IL-2 was used together with 10(3)-10(4) units/ml TNF. TNF alone at any concentration could not mediate the induction of ADCC. Similar to the results obtained in vitro, TNF, when given alone, had no effect on the generation of ADCC in vivo. The addition, however, of TNF to IL-2, given at 10,000 and 20,000 but not 40,000 units, enhanced the IL-2-induced ADCC on a per-cell basis. Furthermore, TNF enhanced the total ADCC activity in various organs including the liver, spleen and thymus as a result of an increase in the number of mononuclear cells isolated from these organs. The increase in total ADCC activity was optimal when 110,000-220,000 units (5-10 micrograms) TNF were employed together with IL-2. The combined treatment with TNF and IL-2 also increased the intracellular benzyloxycarbonyl-1-L-lysine-thiobenzyl-ester esterase content in cells isolated from the livers of mice treated with these cytokines. On the basis of these results we treated mice bearing a single B16 melanoma nodule with TNF and TNF + IL-2 given with or without anti-B16 monoclonal antibody. We found that TNF administration augmented the anti-tumor effect of specific anti-B16 antibodies, and the addition of IL-2 further increased this anti-tumor effect.

Animals↗

PubMed1989

Systemic induction of cells mediating antibody-dependent cellular cytotoxicity following administration of interleukin 2.

We have previously demonstrated that incubation of murine cells in vitro in interleukin 2 (IL-2) induced antibody-dependent cellular cytotoxicity (ADCC) and that these cells were derived from the NK/LAK, FcR+ cell population. In the present study we show that in vivo administration of IL-2 to mice induces cells which exhibit ADCC activity in the peritoneal cavity, liver, lungs, and to a lesser degree in the bone marrow, spleen, mesenteric lymph nodes, and thymus. A gradual increase in ADCC activity and the number of Fc-receptor-positive cells was seen 1 to 3 days after starting IL-2 treatment. The cells mediating ADCC are closely related to LAK cells since they expressed Thy1.2 antigens and are derived from asialo GM1-positive, Lyt2/L3T4-negative, radiosensitive cells. These results demonstrate that IL-2 can systemically induce cells with ADCC activity and that this ability may be useful in the establishment of therapeutic models against disseminated cancer when combined with specific antitumor monoclonal antibodies.

Animals↗

PubMed1989

The effect of various cytokines on the in vitro induction of antibody-dependent cellular cytotoxicity in murine cells. Enhancement of IL-2-induced antibody-dependent cellular cytotoxicity activity by IL-1 and tumor necrosis factor-alpha.

We have previously demonstrated that incubation with IL-2 can induce ADCC activity in murine cells and that this activity was mediated by asialo GM1+, FcR+ cells. In the present study we show that the cytokines IFN-alpha and IFN-gamma, TNF-alpha, and IL-1 alpha are unable to induce antibody-dependent cellular cytotoxicity (ADCC) in murine cells; however, TNF-alpha and IL-1 alpha could substantially augment the ADCC induced by IL-2. IL-1 increased the IL-2-induced ADCC activity in a dose-dependent fashion and in cells isolated from the thymus and spleen. The precursors of the ADCC induced by the combination of IL-1 and IL-2 were asialo GM1+ cells, similar to the precursor cells of IL-2-induced ADCC. The effect of IL-1 and TNF on ADCC was not the result of an increase in the FcR density on the cell surface or the result of an increase in the number of FcR+ cells although IL-1 increased the recovery of viable cells in culture. The main effect of IL-1 and TNF was the enhancement of the lytic ability of the IL-2 cultured cells as indicated by increased intra-cellular benzyloxycarbonyl L-lysine thiobenzylester-esterase activity. These results suggest that lymphokines such as IL-1 and TNF may synergize with IL-2 in the induction of ADCC and could thus potentially be useful for the immunotherapy of established tumors when combined with the administration of specific anti-tumor antibodies.

Animals↗

PubMed1988

Effect of combined therapy with lymphokine-activated killer cells, interleukin 2 and specific monoclonal antibody on established B16 melanoma lung metastases.

We have previously shown that treatment of C57BL/6 mice with specific anti-B16 melanoma monoclonal antibody (Mab) significantly reduced the number of established liver metastases. In this paper we show that when treatment with Mab was applied to mice bearing both liver and lung micrometastases, the number of liver metastases was reduced by 72-98%, whereas no effect was seen on the number of lung metastases. In contrast to results obtained when treating liver metastases, treatment of B16 melanoma lung metastases with Mab and recombinant interleukin 2 was unsuccessful when recombinant interleukin 2 was given concomitantly or after priming with high doses of recombinant interleukin 2. In contrast, when therapy with anti-B16 Mab was combined with the administration of C3H lymphokine-activated killer (LAK) cells, which were shown to exhibit antibody dependent cellular cytotoxicity (ADCC) activity, a significant enhancement in the antitumor efficacy of LAK cells was seen. The inability of C57BL/6 LAK cells, which exhibited low if any ADCC activity to mediate a similar effect, suggested that an ADCC-like mechanism was involved in this therapy. The effect of C3H LAK cells was apparently not the result of administration of allogeneic cells, since fresh C3H splenocytes had no effect on lung metastases when given together with Mab. These findings demonstrate the potential of specific antitumor Mab to affect not only established liver metastases but, when combined with LAK cells that mediate ADCC activity to enhance the eradication of lung metastases as well.

Animals↗

PubMed1988

Heterogeneity of lymphokine-activated killer cells induced by IL-2. Separate lymphoid subpopulations lyse tumor, allogeneic blasts, and modified syngeneic blasts.

Murine splenocytes incubated for 3 to 4 days with the lymphokine, IL-2, acquire the ability to mediate the lysis of a wide variety of fresh tumor targets in short term chromium release assays. We undertook these studies to examine the lysis of splenocyte blasts by these lymphokine-activated killer (LAK) cells, to help gain an understanding of the mechanisms of target cell recognition. Allogeneic blast targets but not syngeneic blasts are highly lysable by LAK effector cells. By using congenic mice, we have shown that only the H-2 haplotype, and not other differences, determines the recognition and lysis of a blast target cell. Both Con A- and LPS-induced allogeneic splenocyte blasts are lysed and thus lectin-induced binding of effectors and targets is unlikely to be responsible for this effect. By using in vivo antibody depletion experiments, we showed that different populations of effector cells mediate the lysis of tumor cells and allogeneic blasts. Furthermore, we observed that the lysis of a susceptible blast can be inhibited only by like cold blasts of the same haplotype. These results suggest that there is a separate population of LAK cells responsible for the lysis of each type of blast target cell. Though syngeneic blasts were not lysed by LAK cells, TNP modification of syngeneic blasts converted them into cells that were recognized and lysed by LAK cells. In cold target inhibition studies, the lysis of fresh syngeneic tumor was not inhibited by TNP-modified syngeneic blasts. Similarly, the lysis of TNP-modified syngeneic blasts was not inhibited by fresh tumor. By using in vitro antibody depletion, we determined that TNP-modified blasts are lysed by LAK cells with Thy-1+ precursors, in distinction to the Thy-1- precursors involved in tumor cell lysis. Elimination of the Thy-1+ cells at the precursor stage completely abrogated the lysis of blasts but did not diminish the lysis of tumor cells. We conclude that IL-2 promotes the growth of numerous populations of effector cells with Thy-1+ precursors that have a narrow range of specificity, in contrast to the broad lytic ability for fresh tumor mediated by LAK cells with Thy-1- precursors.

Animals↗

PubMed1988

Mechanism of protection from graft-vs-host disease in murine mixed allogeneic chimeras. I. Development of a null cell population suppressive of cell-mediated lympholysis responses and derived from the syngeneic bone marrow component.

Splenocyte populations from whole body-irradiated recipients of mixed T cell-depleted (TCD) syngeneic and allogeneic (complete H-2 disparity) bone marrow, or of TCD syngeneic marrow alone, contain cells with the ability to suppress the generation of cell-mediated lympholysis responses in vitro. This activity, which is present by 8 days after bone marrow transplantation and persists for several weeks, has been analyzed for possible veto-like or other specificity. Although reproducible patterns of suppression were observed, depending both on host strain and on the genetic combination of the response examined, the overall suppression in vitro most closely resembles that which has been ascribed to "natural suppressor" cells in other systems. The suppression appears to be mediated by a non-T cell, non-B cell, nonadherent, asialo GM1-negative population. Cold target inhibition and CTL activity of chimeric cells have been ruled out as factors contributing to the observed suppression. Significantly, in mixed chimeras, suppression was found to be mediated exclusively by cells which were syngeneic to the recipient in both recipient strains tested. The rapid development of this suppressive activity may explain the resistance to graft-vs-host disease conferred on whole body-irradiated mice by the addition of TCD syngeneic marrow to an allogeneic graft-vs-host disease-producing inoculum.

Animals↗

PubMed1988

Combined effects of chemotherapy and interleukin 2 in the therapy of mice with advanced pulmonary tumors.

We have evaluated the effects of chemotherapeutic agents on the toxicity and antitumor benefit of therapy of established murine tumors by high-dose interleukin 2 (IL-2). Cyclophosphamide (Cy), doxorubicin, and bischloroethylnitrosourea were given to normal mice prior to IL-2 administration to test the effects of these agents on IL-2-induced toxicity. Cy at doses of 100 mg/kg and 150 mg/kg completely protected mice from a 100% lethal dose of IL-2, and doses of 50 mg/kg and 150 mg/kg allowed the administration of a median of 4.5 and 10.0 more doses of IL-2, respectively, before death from IL-2 toxicity occurred. Doxorubicin at 8 mg/kg and bischloroethylnitrosourea at 20 mg/kg did not impact on toxicity in IL-2-treated mice. In mice bearing pulmonary metastases of the weakly immunogenic MCA-105 sarcoma, IL-2 increased median survival time from 33 (no IL-2) to greater than 60 days for all doses of IL-2 tested when combined with a single injection of Cy at 75 mg/kg (P less than 0.002). Increasing doses of either Cy or IL-2 produced increasing benefits on survival which were always greater than either treatment alone. These effects of Cy and IL-2 were also seen in mice bearing the nonimmunogenic MCA-101 sarcoma and a murine adenocarcinoma (MCA-38). Doxorubicin and bischloroethylnitrosourea did not consistently enhance the effects of IL-2 treatment. Cy appears to reduce the yield of in vivo generated lymphokine-activated killer cells, but these lymphokine-activated killer cells are still lytic for fresh tumor targets in vitro. Thus, the mechanism of this synergy does not appear to involve stimulation of lymphokine-activated killer cell activity, but may in part involve reduction of tumor burden by the chemotherapeutic agent, an increase in susceptibility of tumor to cellular immune lysis, and/or a decrease in suppressor cell activity mediated by the chemotherapy.

Animals↗

PubMed1988

Characterization of IL-2-induced murine cells which exhibit ADCC activity.

The incubation of murine splenocytes in recombinant interleukin 2 (IL-2) gives rise to both lymphokine-activated killer (LAK) cells capable of lysing fresh tumor cells and cells capable of mediating antibody-dependent cellular cytotoxicity (ADCC) in the presence of anti-H2 allosera. A similarity between these two IL-2-induced cell populations was found. The precursors of the cells mediating these activities were shown to be ASGM1 positive, Thy 1 negative, and radiosensitive. Cells taken from the spleen, thymus, and bone marrow were able to mediate ADCC after culture in IL-2. The effector cell was either Thy 1 positive or negative and was less affected by anti-Thy 1 plus C' treatment than cells which mediated LAK activity. In addition ADCC was exhibited in IL-2-cultured splenocytes from various murine strains and correlated with their LAK activity with one exception. While IL-2-cultured C57BL/6 splenocytes exhibited LAK activity similar to that of C3H LAK cells, no ADCC activity could be demonstrated in C57BL/6 cells. Study of the difference in the ability of these two strains to mediate ADCC revealed that IL-2-induced FcR+ cells in C3H thymocytes, but not in C57BL/6 thymocytes. Based on FACS analysis and on the radiosensitivity of the induction of both FcR+ cells and ADCC, it was suggested that IL-2 was expanding a small FcR+ cell population rather than inducing an increase in FcR density on the cell surface. The relationship between the IL-2-induced ADCC mediator and other IL-2-induced cells, as well as ADCC effector cells, and the possible implications of the results for the in vivo therapy of cancer based on ADCC are discussed.

Animals↗

PubMed1987

Effect of anti-B16 melanoma monoclonal antibody on established murine B16 melanoma liver metastases.

The administration of anti-B16 monoclonal antibody of the IgG2b isotype to mice bearing established B16 melanoma liver metastases caused a significant and consistent reduction of up to 90% in the number of these metastases. No reduction in the number of metastases was noted when antigenically unrelated tumor or nonspecific immunoglobulin were employed. The antibody-mediated antitumor effect was completely abrogated by total body irradiation of the host. Treatment of the tumor-bearing host with antiserum directed against asialo GM1 prior to anti B16 antibody administration, abrogated the therapeutic effect indicating the involvement of a radiosensitive, ASGM1-positive cell in the tumor regression. The antitumor effect of the antibody treatment could be augmented by the concomitant administration of recombinant interleukin-2. The effect seen may have possible application in the treatment of liver metastases in humans by combined immunotherapy using recombinant interleukin-2 and specific antitumor monoclonal antibodies.

Animals↗

PubMed1987

Antibody-dependent cellular cytotoxicity mediated by murine lymphocytes activated in recombinant interleukin 2.

The incubation of murine splenocytes in recombinant interleukin 2 (RIL 2) gives rise to lymphokine-activated killer (LAK) cells that can lyse fresh, NK-resistant tumor cells but not normal cells in 4-hr 51Cr-release assays. Lysis by this IL 2-activated cell population was enhanced up to 100-fold by prior reaction of target cells with specific antisera reactive with antigens on the target cells. This antibody-dependent cellular cytotoxicity (ADCC) also resulted in lysis of fresh normal target cells, which are not usually susceptible to LAK lysis. The ADCC was evident after 24 hr of incubation of splenocytes in RIL 2, but peak lytic activity was reached after 3 to 4 days of incubation. The concentrations of RIL 2 needed for the in vitro activation of the effectors in order to attain maximal ADCC was between 100 and 3000 U/ml and parallel the IL 2 concentrations required to generate LAK cells. ADCC mediated by IL 2-activated splenocytes was completely blocked by anti-FcR monoclonal antibodies. Although antisera directed against MHC antigens were used in most experiments, anti-B16 monoclonal antibodies have also shown the ability to induce ADCC mediated by RIL 2-activated syngeneic and allogeneic cells. Treatment of the precursor splenocyte populations with anti-asialo GM1 and complement eliminated the direct LAK activity and the antibody-dependent cytotoxicity, suggesting that both direct and indirect tumor cell lysis may be caused by the same effector cell. ADCC mediated by LAK cell populations represents another possible mechanism for the in vivo therapeutic effects of these cells.

Animals↗

PubMed1986

The effect of cimetidine on PBL from healthy donors and melanoma patients: augmentation of T cell responses to TCGF mitogens and alloantigens and of TCGF production.

The effect of cimetidine, an H-2 receptor antagonist, on activation of PBL from both normal individuals and melanoma patients was studied. It has been shown that cimetidine enhanced, though moderately, the production of TCGF from normal PBL after PHA-P stimulation. In addition, cimetidine significantly augmented TCGF-induced proliferation of normal PBL, as well as proliferation induced by allogeneic cells (MLC) by PPD, Con A, and PHA. In PBL samples where coincubation with cimetidine had limited or no effect, preincubation of PBL with cimetidine prior to the addition of IL-2 and other T cell activators showed a significant enhancement effect. This effect mediated by cimetidine was further demonstrated on PBL from melanoma patients whose T cell responses were initially low. The possibilities are discussed that: (a) cimetidine treatment inactivates suppressor cell activity, thus enhancing T cell mediated responses; or (b) cimetidine may act directly at effector cell level.

Cells, Cultured↗