Differential responsiveness of various substrains of inbred strain 2 guinea pigs to immunotherapy with the methanol extraction residue (MER) of BCG

Wainberg, Mark A.; Margolese, Richard G.; Weiss, David

doi:10.1007/bf00200055

Cited by 6 publications

(4 citation statements)

References 28 publications

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“…The recent discoveries that viruses (8) and glucocorticoids (9) induce immunosuppression by interfering with IL-2 production suggest that administration of IL-2, and possibly other factors, may be effective in enhancing immunity in compromised animals. However, one of the current limiting factors impeding the investigation of such possibilities is the lack of an adequate supply of the scarce authentic bovine IL-2 lymphokine necessary for extensive experimental studies, although research on the bovine protein has begun (10).…”

mentioning

confidence: 99%

Molecular cloning of a functional bovine interleukin 2 cDNA.

Reeves¹,

Spies²,

Nissen³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

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A cDNA clone of the bovine interleukin 2 (IL-2) gene has been isolated and demonstrated to be functional in the production of secreted bovine IL-2 protein when transfected into monkey cells. The bovine IL-2 clone is 791 base pairs in length and contains an open reading frame of 474 base pairs coding for a bovine IL-2 precursor polypeptide of 158 amino acids with an estimated molecular weight of 17,884. The putative hydrophobic leader or signal sequence of the precursor protein is 23 amino acid residues long, suggesting that, after removal by processing, the mature secreted bovine IL-2 protein contains 135 amino acids and has a molecular weight of 15,464. Comparisons of both the nucleotide sequence and the predicted amino acid sequence of bovine IL-2 with those of the human and mouse IL-2 show extensive regions of sequence conservation between the species, interspersed with other regions of less siilarity. The 3' untranslated region of the bovine IL-2 gene shares as much, if not greater, sequence homology with the 3' untranslated regions of the human and mouse genes as do the transcribed coding regions of these genes, suggesting an involvement of this region in regulation. In particular, a tandemiy repeated sequence, (TATT)., found in the 3' untranslated tail of the bovine IL-2 done is also found in the 3' untranslated region of the other known interleukin and interferon genes, as well as in similar regions of many other inducible genes of the lymphoid and immune response systems, suggesting a cdej or tissue-spevific regulatory function for these evolutionarily conserved sequences.

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mentioning

confidence: 99%

Molecular cloning of a functional bovine interleukin 2 cDNA.

Reeves¹,

Spies²,

Nissen³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

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“…MER can prolong survival following chemotherapy or radiotherapy of experimental tumors, al, though it usually does not produce cures [76]. The mechanism of action of MER is similar to that of BCG but, as has been mentioned, it is a far less potent inducer of tuberculin sensitivity than BCG.…”

Section: Nonviable Derivatives Of Bcgmentioning

confidence: 94%

“…The percentage of animals cured by MER immunotherapy has been Iess than that cured by viable BCG or BCG cell walls mixed with mineral oil. This difference may be due in part to the BCG-line-10 shared antigen phenomenon, and the fact that MER is a far less potent inducer of tuberculin sensitivity than BCG [76]. In the iine-10 guinea pig hepatoma model, intralesional injection of MER was necessary for efficacy, in contrast to other tumor models in which MER has been as effective, or more effective, by distal administration [77J.…”

Section: Nonviable Derivatives Of Bcgmentioning

confidence: 99%

“…In contrast, neither pretreatment with BCG nor injection with BCG at sites distal to the growing tumor proved effective [57]. However, the immunoprotective effect of MER could not be duplicated if a different strain-2 guinea pig Substrain was employed [76]. The percentage of animals cured by MER immunotherapy has been Iess than that cured by viable BCG or BCG cell walls mixed with mineral oil.…”

Section: Nonviable Derivatives Of Bcgmentioning

confidence: 99%

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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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Effects of therapeutic treatment with the MER tubercle bacillus fraction on Rous sarcomas of chickens induced by the Rous sarcoma virus

Markson¹,

Weiss

1980

Cancer Immunol Immunother

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Differential responsiveness of various substrains of inbred strain 2 guinea pigs to immunotherapy with the methanol extraction residue (MER) of BCG

Abstract: Summary. The immunotherapeutie effects of the methanol extraction residue (MER) of

Cited by 6 publications

References 28 publications

Molecular cloning of a functional bovine interleukin 2 cDNA.

Molecular cloning of a functional bovine interleukin 2 cDNA.

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

Effects of therapeutic treatment with the MER tubercle bacillus fraction on Rous sarcomas of chickens induced by the Rous sarcoma virus

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