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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral blood lymphocytes (PBL) stimulated by interleukin-2 (IL-2) for 48-96h, generated killer cells against the human colon cancer cell line SW948. The killing capacity increased significantly when the specific mouse monoclonal antibody (MAb) 17-1A was present during the lytic process. The chimeric antibody 17-1A determined a significantly stronger cytotoxicity compared to mouse MAb 17-1A. MAb BR55-2 which recognizes a different antigen on SW948 target cells mediated a similar cytotoxicity as MAb 17-1A. Presence of alpha-interferon (IFN) during the lytic assay significantly enhanced the killing of the tumor by lymphokine activated killer (LAK) cells as well as by LAK cells and mouse MAb 17-1A. However, when chimeric MAb 17-1A and LAK cells were used alpha-IFN failed to increase the lytic activity, probably due to already maximum lysis in the system. Combinations of various biological response modifiers such as monoclonal antibodies, IL-2/LAK cells and alpha-IFN carry great promise to improve this kind of therapy for cancer patients.
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PMID:Lymphokine activated killer (LAK) cells in antibody dependent cellular cytotoxicity (ADCC) using MAb 17-1A: a combination of potential usefulness in tumor therapy. 280 10

Activated killer cells are generated by the incubation of peripheral blood mononuclear leukocytes (PBL) in the lymphokine interleukin 2 (IL-2). Unseparated populations of these lymphokine-activated killer (LAK) cells lyse a variety of fresh noncultured human tumor targets, but they do not kill normal PBL. This study analyzed the generation and lytic specificity of LAK cell clones. Of 49 (84%) clones isolated by limiting-dilution techniques from a whole population of LAK cells, 41 manifested significant LAK cell activity. LAK cell clones had varied cell surface phenotypes. Clones with high and intermediate LAK cell activity were Leu 2+3-4+7-DR+Tac+ and Leu 2-3+4+7-DR+Tac+, respectively. Single LAK cell clones lysed multiple fresh human tumor targets including autologous sarcoma, 5 allogeneic sarcomas, and a colon cancer in addition to the cultured cell line K562. Autologous PBL were not lysed. Tumor targets were each lysed by multiple LAK cell clones. Sixteen subclones were derived from 5 of these LAK cell clones. These subclones had 99% or greater probability of being derived from a single cell. These subclones also exhibited lysis of multiple tumor targets. These findings suggest the existence of a shared determinant, expressed by multiple human tumors, which is recognized in common by multiple LAK cell clones.
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PMID:Lymphokine-activated killer (LAK) cell phenomenon. IV. Lysis by LAK cell clones of fresh human tumor cells from autologous and multiple allogeneic tumors. 298 4

Adoptive immunotherapy with interleukin 2 (IL-2) and lymphokine-activated killer (LAK) cells (IL-2/LAK) is a technically demanding cancer therapy dependent upon large scale isolation and culture of lymphocytes. An important question is whether this technology can be accomplished routinely outside of highly specialized centers. In addition, no systematic examination of laboratory correlates of IL-2/LAK therapy in humans has been reported to date. The objectives of this report are to address two issues relevant to IL-2/LAK therapy. (a) Can IL-2/LAK therapy be accomplished outside of previously identified centers of expertise? (b) What are the relevant laboratory/clinical parameter correlations? The six institutions in the National Cancer Institute extramural trial treated 83 evaluable patients with renal cancer, malignant melanoma, or colon cancer with IL-2/LAK by a uniform protocol. Patients received 5 days of IL-2 priming, then daily leukaphereses for 5 days starting 48 h after IL-2 to harvest cells. Mononuclear cells were isolated, then cultured in roller bottles in 1-liter aliquots for 3 to 4 days at a cell density of 1.5 x 10(6) per ml with recombinant IL-2, 1500 units per ml. Cells were harvested and administered to patients with additional IL-2. Administration of IL-2 regularly induced lymphopenia and rebound lymphocytosis. Leukapheresis yields and numbers of LAK cells generated in culture and reinfused into patients correlated directly with peak lymphocyte counts achieved by IL-2 administration. Mean mononuclear cell recovery per 5 days of leukapheresis (+/- SEM) was 14.3 +/- 0.8 x 10(10). Average volume of cells cultured per patient was 95 liters (range, 41 to 235). Mean yield of cells harvested from cultures was 53%. Mean total number of LAK cells infused per patient was 7.6 +/- 0.4 x 10(10) (range, 2 to 15.2 x 10(10]. LAK activity was measured in vitro by lysis of 51Cr-labeled natural killer-resistant Daudi and fresh tumor targets. LAK effector cells regularly lysed these targets in vitro. Neither tumor reduction nor clinical toxicity correlated with dose or with cytolytic activity of LAK cells, or with other laboratory parameters including base-line lymphocyte count and IL-2-induced lymphocytosis. We conclude: (a) large quantities of LAK effector cells with tumoricidal activity can be generated routinely at different centers; (b) neither in vitro LAK activity nor numbers of LAK cells infused were predictive of clinical efficacy or toxicity. There is a need to identify other laboratory or clinical parameters more predictive of IL-2/LAK therapeutic efficacy or toxicity.
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PMID:Laboratory correlates of adoptive immunotherapy with recombinant interleukin-2 and lymphokine-activated killer cells in humans. 326 May 37

We studied a series of 40 rats at various stages of colorectal carcinoma, as induced by N-methyl-N-nitro-Nitrosoguanidine. Lymphokine containing supernatants were obtained simultaneously from splenic and peripheral lymphocytes, after exposure to rat colon cancer antigen in vitro. The lymphokine was found capable of performing Macrophage Migration Inhibition (MIF) when obtained from rats with: carcinoma through serosa, carcinoma of submucosa, carcinoma of the mucosa and carcinoma in situ. All control rats were free of cancer and were MIF negative. The MIF response in this study was evaluated as a marker of chemically induced colorectal carcinoma in rats in order to better understand the lymphocyte response to tumor progression from atypia to adenocarcinoma of the colon.
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PMID:Colon cancer bearing rats produce a lymphokine which induces macrophage migration inhibition (MIF) in vitro. 328 27

Patients with colorectal cancer respond poorly to in vivo immunotherapy with lymphokine-activated killer (LAK) cells generated from peripheral blood mononuclear cells (PBMC). We postulated that gut-derived immune cells could be a more relevant source of LAK cells directed against colorectal cancer. Intestinal lamina propria mononuclear cells (LPMC) and colonic adenocarcinoma cells were isolated from operative specimens by combination of mechanical and enzymatic dissociation methods. LAK cells were generated by culturing PBMC and LPMC with recombinant interleukin 2 (IL2), with and without OKT3 monoclonal antibody, in short- (4 days) and long-term (21 days) cultures. Other cultured tumor cells, normal intestinal fibroblasts, and hapten-modified autologous LPMC were used as control targets. Cytotoxicity was measured by a 4-hr 51Cr release assay. Short-term cultured LAK cells exhibited a strong to moderate degree of killing against normal intestinal fibroblasts, hapten-modified self cells, and four different tumor cell lines. Instead, fresh colon cancer cells were resistant to cytotoxicity, regardless of their degree of histologic differentiation and the autologous or allogeneic nature of the LAK cells. Long-term culture with IL2 remarkably increased LAK cell activity against all tumor targets, but not against colonic adenocarcinoma cells. The results of this study, showing that freshly isolated colon cancer cells are intrinsically resistant in vitro to highly activated cytotoxic effector cells, may explain the poor clinical results observed in human trials with in vivo administration of IL2 or LAK cells.
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PMID:Lymphokine-activated killer (LAK) cells from human intestinal mucosa: cytotoxic activity against tumor cell lines and modified self but not autologous and allogeneic colon cancer cells. 336 87

Abdominal operations induce immunosuppression during the time when tumors are manipulated and tumor cells are released into the circulation. The authors tested the hypothesis that the combined effect of these factors may promote the development of metastatic tumor implants and that perioperative treatment with Human Recombinant Interleukin-2 (RIL-2), a known immunostimulant of t, natural killer (NK), and lymphokine activated killer (LAK) cells may reduce the incidence of liver metastases from transplantable rat colon cancers. Hepatic metastases were induced in male Fischer 344 (F344) rats by injecting 10(7) rat colon tumor cells into the portal venous system during laparotomy. Control rats developed tumors by four weeks and were dead by ten weeks. Eleven groups of rats underwent celiotomy with portal vein injection of tumor on day three. Rats received either no RIL-2, RIL-2, or excipient buffer at varying doses on days 1 through 5 or 3 through 7 of these experiments. Animals were assessed for the presence of tumor and the incidence of liver metastases at autopsy (sacrifice and autopsy performed at seven weeks). Eighty-five percent of the rats in the untreated group developed tumor. This compared with only 50 percent of animals receiving 10(3) u/dose (P less than .025) and 42 percent of animals receiving 10(4) u/dose (P less than .01) of Interleukin-2 on days 1 through 5. Animals receiving very high doses of RIL-2 (10(5) or 4 X 10(5) units per dose) had a greater chance of developing tumors than did control rats, or rats receiving lower doses of RIL-2 (P less than .05). It is concluded that the perioperative period may be critical for the implantation and growth of metastatic disease and that perioperative immunostimulation with RIL-2 can decrease the incidence of tumors in these animals. This model may have relevance to the treatment of human colon cancer.
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PMID:Reduced incidence of hepatic metastases by perioperative treatment with recombinant human interleukin-2. 349 96

We describe here the preliminary results of the systemic administration of autologous lymphokine-activated killer (LAK) cells and the recombinant-derived lymphokine interleukin-2 to patients with advanced cancer. This regimen was based on animal models in which the systemic administration of LAK cells plus interleukin-2 mediated the regression of established pulmonary and hepatic metastases from a variety of murine tumors in several strains of mice. We treated 25 patients with metastatic cancer in whom standard therapy had failed. Patients received both 1.8 to 18.4 X 10(10) autologous LAK cells, generated from lymphocytes obtained through multiple leukaphereses, and up to 90 doses of interleukin-2. Objective regression of cancer (more than 50 per cent of volume) was observed in 11 of the 25 patients: complete tumor regression occurred in one patient with metastatic melanoma and has been sustained for up to 10 months after therapy, and partial responses occurred in nine patients with pulmonary or hepatic metastases from melanoma, colon cancer, or renal-cell cancer and in one patient with a primary unresectable lung adenocarcinoma. Severe fluid retention was the major side effect of therapy, although all side effects resolved after interleukin-2 administration was stopped. Further development of this approach and additional patient follow-up are required before conclusions about its therapeutic value can be drawn.
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PMID:Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. 390 8

Normal human globulin fraction 1 (NHG-1) produced cytotoxicity and/or cytostasis as well as inhibition of protein synthesis in 8 well-characterized human tumor cell lines (4 breast cancer, 1 colon cancer, 1 melanoma, and 2 leukemia) and in 2 variants of murine B-16 melanoma. NHG-1 was not cytotoxic for the Chang liver cell line, a normal kidney embryo line, or for normal lymphocytes or macrophages when used in lower concentrations but was growth inhibitory for normal cells in higher concentrations. Although lymphocyte blastogenesis with phytohemagglutinin (PHA) was inhibited by high concentrations of NHG-1, augmentation of the lymphocyte PHA response was seen at lower concentrations, suggesting a lymphokine-like effect. Preincubation with the mitogen partially nullified these NHG-1 effects (suggesting the need for cell surface binding). Although NHG-1 antitumor activity was confirmed in selected human and murine tumor cell lines, the mechanism of its activity is unknown. Occurrence of NHG-1 in the alpha 2-globulin region (an area rich in immune-regulating factors) suggests that NHG-1 may have general "cytokine"-like effects and may be capable of regulating replication of both normal and transformed cells.
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PMID:Antitumor effects of a normal human serum factor (normal human globulin fraction 1) on human tumor cells in vitro. 619 42

By means of the macrophage electrophoretic mobility technique we could show lymphocytes of patients suffering from cancers of the digestive system to be sensitized to carcinoembryonic antigen (CEA). These findings conflict with the common view that CEA is not immunogenic in humans. The aim of the present study was to look as to whether conventional anti-CEA sera can neutralize the activity of a CEA preparation which is responsible for the human lymphocyte response. When 60 ng CEA were preincubated with highly diluted anti-CEA serum and the resulting immune complexes were thereafter co-precipitated by protein A-sepharose, positive lymphocyte responses could no longer be obtained. This effect was observed with 3 anti-CEA sera in 3 cancer patients (colon cancer, stomach cancer, teratocarcinoma), who's lymphocytes responded to CEA by lymphokine release. Normal serum had no neutralizing effect. The anti-CEA sera did not influence the activity of another tumour-relevant extract (teratocarcinoma-derived), to which cancer patients' lymphocytes reacted regardless of the tumour site. The lymphocytes from an oesophagus carcinoma patient, though reacting to the teratocarcinoma preparation, did not respond to CEA, thus, logically, all other tests with normal serum and anti-CEA sera were negative, too. The results show that the digest system cancer-associated lymphocyte reactivity to CEA can be abrogated by conventional anti-CEA sera, which finding indicates that there exist closely CEA-associated "tumour-specific" antigenicities.
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PMID:Sensitization of human lymphocytes to carcinoembryonic antigen (CEA): neutralization experiments with anti-CEA sera. 707 17

Pokeweed mitogen (PWM) was found to induce rapidly killer cells in human peripheral blood mononuclear cells (PBMC). To avoid PWM contamination in infused lymphocytes, PBMC were stimulated with PWM-coated beads, CMC-1. One hour of stimulation with CMC-1 led to distinct cytotoxic activity in PBMC at 7 h, this reaching a peak at 23 h in the following in vitro culture. The cytotoxic activity and target cell spectrum of CMC-1-activated killer (PWM-AK) cells were similar to those of lymphokine-activated killer (LAK) cells, the precursor cells of PWM-AK cells, as are those of LAK cells which are also low-density lymphocytes. The in vivo antitumor effects of PWM-AK cells were examined in nude mice with peritoneal carcinomatosis generated by the human colon cancer cell line, RPMI 4788. The intraperitoneal (i.p.) injection of PWM-AK cells immediately after stimulation with CMC-1 significantly prolonged the survival of tumor-bearing mice, suggesting that these cells could be of value for clinical cancer therapy.
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PMID:Lectin-activated killer cells rapidly induced by pokeweed mitogen conjugated beads and their in vivo antitumor effects. 780 34


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