In vitro assays of immunocompetence in patients with lung cancer treated with levamisole

Golub, Sidney H.; Holmes, E. Carmack

doi:10.1007/bf00199191

Cited by 6 publications

(4 citation statements)

References 10 publications

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“…One such agent that has generated interest is BCG. Intralesional injection of BCG as immunotherapy has been associated with spontaneous regression of tumors and local augmentation of cellular immune responses including NK activity [ 13,15,16].…”

Section: Introductionmentioning

confidence: 99%

Effects of intralymphatic immunotherapy on natural killer activity in malignant melanoma patients

Moy

Golub²,

Calkins³

et al. 1985

Journal of Surgical Oncology

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Adjuvant immunotherapy has the theoretical attraction of augmenting the host immune response at a time when the tumor burden is low. We have previously reported that intralymphatic immunotherapy (ILI) augments the cytolytic humoral immune responses in melanoma patients. This study was undertaken to assess the effects of ILI on cell-mediated immunity. As a model for the cellular effects of ILI, we investigated the natural killer (NK) cell activity in malignant melanoma patients. Fourteen patients were given an allogeneic cultured tumor cell vaccine (TCV) intralymphatically with concomitant administration of BCG. Natural killer cell activity was assessed sequentially using the single cell lysis and binding assay. Overall NK activity against the K562 target cell line showed a moderate increase over pretreatment levels as reflected by the increased number of target binding lymphocytes. However, the percentage of target binders mediating cell lysis remained unchanged during treatment. Assessment of NK activity against the NK-resistant M14 melanoma cell line reflected similar findings. These results suggest the activation of NK cells by tumor antigens, BCG, and/or alloimmunization with TCV. This increase appears to be manifested by increased target recognition rather than by alterations in effector cell function.

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Section: Introductionmentioning

confidence: 99%

Effects of intralymphatic immunotherapy on natural killer activity in malignant melanoma patients

Moy

Golub²,

Calkins³

et al. 1985

Journal of Surgical Oncology

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“…In view of the dissociation between various in vitro and in vivo tests of immunocompetence [46,47], there is clearly a need to develop a more meaningful immunological or serological method of assessing the effect of BCG and other immune modulators on the host immune system, and to correlate this with the in vivo effects on the tumor. The problem is comparable to using anticoagulant therapy without being able to monitor serial changes in the coagulation profile, and to institute necessary dosage adjustments as indicated.…”

Section: Discussionmentioning

confidence: 99%

“…The overall data to date indicate a complex and rather poorly understood situation. A dissociation in the correlation of in vivo and in vitro assays of immunocompetence in cancer patients has been reported by different groups [46,47], further emphasizing the complexity of immunological monitoring. Furthermore, augmentation of delayed-type hypersensitivity responses to recall antigens, over and above that seen with BCG, by utilizing transfer factor did not improve the therapeutic results in disseminated malignant melanoma treated with combination chemoimmunotherapy (M. A. Schwarz et al, manuscript in preparation).…”

Section: Immunological Effectsmentioning

confidence: 96%

Immunotherapy and chemoimmunotherapy of malignant disease with BCG and nonviable mycobacterial fractions

et al. 1977

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The administration of Bacillus Calmette‐Guérin (BCG) has been associated with restoration of general immunocompetence, augmentation of specific tumor immunity, activation of local and regional host defense mechanisms, and stimulation of the reticuloendothelial system. There is evidence that antigens from a variety of unrelated tumors are shared with, or are similar to, antigens in BCG. However, it is uncertain whether this cross‐reactivity is the basis for the antitumor activity of BCG. Numerous studies emphasize the importance of regional effects of immunotherapy. They suggest a two‐step mechanism for antitumor activity that involves recognition of BCG by host defense mechanisms, followed by activation and mobilization of macrophages by specifically produced lymphokines. The several nonviable derivatives of BCG have activity comparable to BCG without many of the problems associated with viable BCG. An optimal, completely standardized BCG preparation has not yet been produced. Clinical studies on the immunotherapeutic effects of BCG and its derivatives in cancer patients indicate that in cutaneous malignant melanoma, intralesional injection of BCG causes complete regression of tumor in 65–90% of instances, with long‐term remission in patients with purely cutaneous metastatic disease. In patients with disseminated malignant melanoma, studies show prolongation of remission duration and overall survival in patients undergoing chemoimmunotherapy (with BCG + imidazole carboxamide) over those receiving chemotherapy alone. In acute lymphoblastic leukemia, one study has found a greater than 90% probability of survival in patients with the microlymphoblastic type undergoing immunotherapy after 5 years, yet other studies fail to show any therapeutic advantage. In most studies in acute myeloblastic leukemia, immunochemotherapy has given both qualitative and quantitative improvements in remission duration and particularly survival. Increased survival, particularly in stage I patients, has been reported in a trial of adjuvant BCG immunotherapy in lung cancer. Other studies on carcinoma of the colon, breast, and the head and neck, soft tissue sarcomas, and genitourinary cancers, utilizing various combinations of BCG and its derivatives, and chemotherapy, surgery, or radiation therapy indicate enhanced remission duration and survival. However, more research is needed to determine the optimum therapy combination in each case, to make refinements in dose, route, and schedule of administration, to improve product characteristics, and to overcome the complications of BCG immunotherapy.

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“…Levamisole, an oral antihelminthic drug, is considered an immunoreconstituting agent or an antianergic agent, 5,6,17,21,35,36,53,73,123,128 It restores depressed immune responses to normal, although it does not stimulate them to a level above the norm. 6 Primarily affected are host defense cells that have the capacity to circulate and thus are able to enter the invaded areas of the body to eliminate the invading cells.…”

Section: Levamisolementioning

confidence: 99%

Immunotherapy of Lung Cancer

Matthay¹

1982

Semin Respir Crit Care Med

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In vitro assays of immunocompetence in patients with lung cancer treated with levamisole

Cited by 6 publications

References 10 publications

Effects of intralymphatic immunotherapy on natural killer activity in malignant melanoma patients

Effects of intralymphatic immunotherapy on natural killer activity in malignant melanoma patients

Immunotherapy and chemoimmunotherapy of malignant disease with BCG and nonviable mycobacterial fractions

Immunotherapy of Lung Cancer

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