Spectrum and Mode of Action Of Poly A: U in the Stimulation of Immune Responses

Braun, Werner; Ishizuka, Masaaki; Yajima, Y; Webb, David R.; Winchurch, Richard A.

doi:10.1007/978-3-642-85772-0_10

Cited by 40 publications

(14 citation statements)

References 21 publications

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“…The synthetic polynucleotide poly(A * U), a known enhancer of humoral and cell-mediated immune responses (13)(14)(15), was added in different concentrations to cultures of mouse spleen cells (16) that contained sheep erythrocytes as antigen. Fig.…”

Section: Resultsmentioning

confidence: 99%

Antibody Formation: Reduced Responses After Administration of Excessive Amounts of Nonspecific Stimulators

Braun¹,

Ishizuka²

1971

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

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Enhancement of antibody formation in vitro and in vivo by poly(A U), cyclic AMP, dibutyryl cyclic AMP, or any one of these agents in combination with theophylline or caffeine, is usually limited to certain dose ranges. High doses of these nonspecific stimulators can produce less or no enhancement, or may actually inhibit antibody formation. Such dose-response relationships may be pertinent to an understanding of phenomena of specific immunological nonresponsiveness and certain types of antigenic competition.

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Section: Resultsmentioning

confidence: 99%

Antibody Formation: Reduced Responses After Administration of Excessive Amounts of Nonspecific Stimulators

Braun¹,

Ishizuka²

1971

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

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“…It has been shown to posses an antitumor effect, and to be a potent immunomodulator of both the humoral and cellular immune response and to result in enhancement of natural killer (NK) cell activity [1,3,11,12,24). Furthermore, even at high dosage, no toxic or pyrogenic effects have been reported on use of poly A-poly U as an adjunct in cancer therapy [4,8].…”

Section: Offprint Requests To: S K Singhmentioning

confidence: 99%

Abrogation of the tumor promoting effect of allogeneic blood transfusion by polyadenylic-polyuridylic acid (poly A-poly U)

Singh

Marquet

Westbroek

et al. 1987

Cancer Immunol Immunother

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Studies from several centers have shown an immunosuppressive effect of surgical procedures, whilst others have shown blood transfusion in association with cancer surgery to have an adverse effect on ultimate prognosis. We have previously demonstrated enhanced growth of tumor metastases, in rats following allogeneic blood transfusion and surgery. Polyadenylic-polyuridylic acid (poly A-poly U) has been reported to stimulate immune responses. In this report, we have investigated the effectiveness of poly A-poly U as an adjuvant to blood transfusion and surgical procedures in BN rats bearing artificial lung metastases. Significantly reduced tumor growth was observed, following poly A-poly U adjuvant treatment. These results lead to serious contemplation of the use of this drug as adjuvant therapy in blood transfused and surgically treated patients.

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“…Subsequently, Braun and colleagues, guided both by their previous extensive studies showing that oligonucleotides could stimulate division in bacterial cells and by their insight, postulated that mammalian antibody synthesis might require endogenous stimulatory molecules of a similar nature. They recognized and tested the potential of the then newly developed (1965) synthetic doublestranded polyribonucleotides (12). Their demonstration that poly(I) -poly(C) and poly(A) * poly(U) complexes were capable of increasing the numbers of antibody-forming cells fourto fivefold caused interest to focus rapidly on these synthetic complexes because of their defined structure and ready availability.…”

Section: Polyribonucleotide Complexesmentioning

confidence: 99%

Molecular adjuvants and immunomodulators: new approaches to immunization

Johnson

1994

Clin Microbiol Rev

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Epitopes on microbial antigens responsible for protective immunity have begun to be identified and isolated, and their chemical structures have been determined. Ensuing knowledge of their weak immunizing capacity per se has led to an appreciation of the need for adjuvants to increase the immunogenicity of these low-molecular-weight synthetic structures. As such, a recent surge in adjuvant research has emerged. Accordingly, this review will highlight a number of those adjuvant substances whose activity in animals indicates a potential use in human vaccines. In addition, the potential of several well-defined substances, termed immunomodulators, which nonspecifically stimulate resistance of animals to multiple 50% lethal doses of microbial challenge is described. Among the most extensively characterized adjuvants of microbial origin discussed in detail are (i) the lipopolysaccharides isolated from gram-negative bacteria and their nontoxic analogs, (ii) the synthetic muramyl dipeptides and their multiple analogs, and (iii) the synthetic polyribonucleotide complexes, mimicking the interferon-inducing capacity of viruses. Discussed also are the heat-labile enterotoxin of Escherichia coli, the nonionic block copolymers, the saponins, a quinolamine derivative, and the hormone dihydroepiandrosterone.

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Spectrum and Mode of Action Of Poly A: U in the Stimulation of Immune Responses

Cited by 40 publications

References 21 publications

Antibody Formation: Reduced Responses After Administration of Excessive Amounts of Nonspecific Stimulators

Antibody Formation: Reduced Responses After Administration of Excessive Amounts of Nonspecific Stimulators

Abrogation of the tumor promoting effect of allogeneic blood transfusion by polyadenylic-polyuridylic acid (poly A-poly U)

Molecular adjuvants and immunomodulators: new approaches to immunization

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