Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A randomized controlled study of immunotherapy with interleukin 2 (IL-2) and lymphokine-activated killer (LAK) cells was conducted in 105 patients after noncurative resection of primary lung cancer. Half the patients received only the standard postoperative radiation therapy or chemotherapy (control group). The other half received immunotherapy with IL-2 and LAK cells in addition to the standard therapy (immunotherapy group). The primary endpoint was survival. The 7-year survival rate was greater in the immunotherapy group than in the control group (39.1% vs. 12.7%, P < 0.01). Among patients with squamous cell carcinoma, there was no statistical difference in outcome. In contrast, the 7-year survival rate among patients with adenocarcinoma in the control group was only 5.2% but for those in the immunotherapy group it was 38.9% (P < 0.05). If resection was noncurative because of pulmonary metastasis, residual cancer or incomplete resection of lymph nodes, then immunotherapy was effective. If resection was noncurative because of residual cancer in the chest wall or diaphragm, or because of carcinomatous pleuritis or pleural dissemination, then there was no statistical difference in survival between the control group and the immunotherapy group.
Lung Cancer 1995 Aug
PMID:Adjuvant immunotherapy with interleukin 2 and lymphokine-activated killer cells after noncurative resection of primary lung cancer. 852 38

This study investigated the generation of primary tumor-specific CTL activity in vitro to several mouse tumors. We report that the development of optimal primary tumor-specific CTL to the P815 mastocytoma, the EL4 thymoma, and the Lewis lung carcinoma is dependent on tumor Ags, on enhancement of T cell costimulation by B7.1, and on exogenous T helper activity in the form of IL-2 and IL-4. A relatively low concentration of IL-2 and IL-4 was required to limit the induction of lymphokine-activated killer cells. In the case of P815, the CTL were directed toward molecularly defined tumor rejection Ags. These primary cultures yielded long term T cell lines that were heterogeneous in fine tumor Ag specificity and in cytokine production.
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PMID:Generation of primary tumor-specific CTL in vitro to immunogenic and poorly immunogenic mouse tumors. 855 87

Out of 642 primary lung cancer patients who underwent surgery between 1986 and 1992, 82 cases who underwent curative resection were enrolled for a randomized prospective controlled study of postsurgical adjuvant immunotherapy using Interleukin 2 (IL-2) and lymphokine activated killer (LAK) cells. From 1986 to 1989 (the initial period), Stage IIIA patients were divided into three groups: group A (chemo-immunotherapy) received IL-2, LAK cell adoptive immunotherapy after two courses of anticancer (CDDP, VDS, MMC) chemotherapy, group B (control) received no adjuvant therapy, and group C (chemotherapy) received the same anticancer chemotherapy as group A. In the latter (1990-1992) period, group C was discontinued because of poor results and Stage II and IIIA cases were randomly assigned to group A or B. The 5- and 7-year survival rates of group A (33 cases) and B (36 cases) were 58.2% and 31.5%, respectively in Stage II and IIIA cases. The prognosis of group A was significantly better than that of group B (P = 0.0038 by the Cox-Mantel (C-M) test and 0.0033 by the generalized Wilcoxon (G-W) test). The 5- and 8-year survival rates of each group for Stage IIIA cases were 53.4% (group A, 25 cases), 33.4% (group B, 26 cases), and 30.8%, 15.3% (group C, 13 cases). The prognosis of group A was significantly better than that of group B (P = 0.045 by the C-M and 0.036 by the G-W test). The difference between group A and B was also significant in N0, N1 (P < 0.01), in T1, T2 (P < 0.01), and T3 (P < 0.05) cases. These results indicate that adjuvant immunotherapy using IL-2 and LAK cells in combination with chemotherapy is significantly effective in improving the postsurgical prognosis of lung cancer patients.
Lung Cancer 1996 Jun
PMID:Adjuvant chemo-immunotherapy after curative resection of Stage II and IIIA primary lung cancer. 879 12

It has recently been shown that the infusion of tumor infiltrating lymphocytes (TIL) and recombinant interleukin-2 (rIL-2) in patients operated on for advanced non-small-cell lung cancer (NSCLC), has significant effects in terms of the survival time and control of local relapses. Despite the evident clinical effects, the treatment is unavailable for patients in which TIL have lost their proliferative potential. In an attempt to identify new sources of effector cells using mixed lymphocyte/tumor cultures (MLTC), populations of peripheral blood (PB) lymphoid cells, which have the capability of lysing autologous NSCLC, were studied at the clonal level. Specific cytolytic lymphocytes were detected at very low frequencies in two out of four patients, whereas non-MHC restricted cytolytic T cells were frequently detected. Cytolytic CD4+ belonged to the Th0 or Th2 subsets and were characterized by cytokine secretion patterns suggestive of a lymphokine cascade that could be involved in cancer control. The identification of different efficient effector mechanisms at the clonal level strongly supports the use of in vitro activated lymphocytes, derived from PB, in protocols of adoptive immunotherapy in patients with advanced NSCLC in which TIL are unavailable.
Lung Cancer 1998 Jul
PMID:Limiting dilution analysis of peripheral blood lymphocytes reacting with non-small-cell lung cancer: functionally heterogeneous effectors efficiently lyse autologous cancer cells. 979 51

Intrinsic or acquired resistance to anticancer drugs necessitated the search for different treatment modalities. The sensitivity of tumor cells to lysis by natural killer (NK) and lymphokine-activated killer (LAK) cells was studied in multidrug resistant (MDR) small cell lung carcinoma (SCLC) by 51Chromium (51Cr) release and conjugate formation assays. The following observations were made: P-glycoprotein positive (P-gp+) MDR SCLC cell line variants were lysed by human LAK cells to a greater extent than were their drug sensitive counterparts. In contrast, P-gp, multidrug resistance protein positive (MRP+) variants of the same line did not exhibit an increased susceptibility to LAK cells. Differential LAK susceptibility is not due to a generalized increase in target fragility to cellular immunity, because NK sensitivity was not increased. Moreover, the P-gp+ MDR SCLC cells showed a higher frequency of binding to LAK cells than did the drug-sensitive parental line. These observations may lead to new insights on combining chemotherapy with immunotherapy.
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PMID:Lymphokine-activated killer cell susceptibility and multidrug resistance in small cell lung carcinoma. 989 92

We conducted a clinical trial of adoptive immunotherapy with lymph node-lymphokine-activated killer (LN-LAK) cells and recombinant interleukin 2 (rIL-2) for a surgical adjuvant therapy of pathologic stage I non-small cell lung cancer. The regimen consisted of the subcutaneous administration of low-dose rIL-2 for 6 consecutive days and the transfer of ex vivo generated LAK cells from regional lymph node lymphocytes, obtained at the time of surgical operation. A group of 19 patients with primary lung cancer received the immunotherapy about 2 weeks after surgery (pulmonary lobectomy). The regimen was postoperatively well tolerated by the patients. In peripheral blood lymphocytes (PBL) obtained after the treatment, the proportion of CD3+ T cells predominantly increased with the increase of CD4+ T cell subsets. On the other hand, the proportion of CD20+ B cells decreased. Both NK and LAK activity of PBL significantly increased. However, the immunomodulatory effects did not result in a prolongation of the postoperative survival time in comparison to the postoperative survival of patients (n = 21) with surgery alone during the same period. These results suggested that the treatment with low-dose LN-LAK cells and concurrent low-dose IL-2 could, therefore, neither reduce nor eradicate minimal micrometastatic diseases.
Lung Cancer 1999 Dec
PMID:Postoperative adjuvant adoptive immunotherapy with lymph node-LAK cells and IL-2 for pathologic stage I non-small cell lung cancer. 1059 24

The effect of adenosine and its analogues on the cytotoxic activity of IL-2-activated NK cells was investigated. Adenosine is an endogenous ligand for four different adenosine receptor (AdoR) subtypes (AdoRA1, AdoRA2A, AdoRA2B, and AdoRA3). Increased concentrations of adenosine were found in ascites of MethA sarcoma or in culture medium of 3LL Lewis lung carcinoma growing under hypoxic conditions. We hypothesize that intratumor adenosine impairs the ability of lymphokine-activated killer (LAK) cells to kill tumor cells. The effect of AdoR engagement on LAK cells cytotoxic activity was analyzed using AdoR agonists and antagonists as well as LAK cells generated from AdoR knockout mice. Adenosine and its analogues efficiently inhibited the cytotoxic activity of LAK cells. CGS21680 (AdoRA2A agonist) and 5-N-ethylcarboxamide adenosine (NECA) (AdoRA2A/ADoRA2B agonist) inhibited LAK cell cytotoxicity in parallel with their ability to increase cAMP production. The inhibitory effects of stable adenosine analog 2-chloroadenosine (CADO) and AdoRA2 agonists were blocked by AdoRA2 antagonist ZM 241385. Adenosine and its analogues impair LAK cell function by interfering with both perforin-mediated and Fas ligand-mediated killing pathways. Studies with LAK cells generated from AdoRA1-/- and AdoRA3-/- mice ruled out any involvement of these AdoRs in the inhibitory effects of adenosine. LAK cells with genetically disrupted AdoRA2A were resistant to the inhibitory effects of adenosine, CADO and NECA. However, with extremely high concentrations of CADO or NECA, mild inhibition of LAK cytotoxicity was observed that was probably mediated via AdoRA2B signaling. Thus, by using pharmacological and genetic blockage of AdoRs, our results clearly indicate the prime importance of cAMP elevating AdoR2A in the inhibitory effect of adenosine on LAK cell cytotoxicity. The elevated intratumor levels of adenosine might inhibit the antitumor effects of activated NK cells.
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PMID:Gs protein-coupled adenosine receptor signaling and lytic function of activated NK cells. 1617 79

Interleukin-2 (IL-2) is a lymphokine produced by T cells whose main function is to stimulate the growth and cytotoxic response of activated T lymphocytes. It has been used to stimulate the immune system for the treatment of multiples tumors. This article is intended to review the reports published from 1990 to 2004 on the IL-2 treatment of tumors other than melanoma and renal carcinoma. A literature search was made in various databases (MEDLINE, EMBASE and BioAssay), focused on IL-2 clinical efficacy in such tumors. A selection was made over 150 publications reporting on administration of IL-2 in multiple tumors: lung carcinoma (small cell and non-small cell), colorectal, gastric, pancreatic, ovarian and breast cancer, sarcomas, hepatocarcinoma, mesothelioma, and brain, urological, and head and neck tumors. IL-2 was mainly used in metastatic disease, associated with other immunotherapy or chemotherapy schedules. We conclude that adjuvant IL-2 may be of value in early stages combined with standard treatment for colon and pancreas cancers. In other neoplasms, the indication for adjuvant IL-2 has been sporadic and does not allow conclusions to be drawn. Assessment of the efficacy of IL-2 combined with chemotherapy as treatment for advanced stages is complex, due to the lack of a control, and the variety of dosages and schemes. The activity of IL-2 in monotherapy or in association with immunotherapy is clinically relevant in hepatocarcinoma, mesothelioma and in malignant overflows as palliative treatment. Randomized trials would be required in order to be able to draw conclusions about its indication in other tumors.
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PMID:Interleukin-2 for the treatment of solid tumors other than melanoma and renal cell carcinoma. 1631 84


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