Peptides as requirement for immunotherapy of the guinea-pig line-10 tumor with endotoxins

Ribi, Edgar; Parker, R.; Strain, S. M.; Mizuno, Yusuke; Nowotny, Alois; Eschen, Kenneth B. Von; Cantrell, John L.; McLaughlin, Charles A.; Hwang, Ki Won; Goren, Mayer B.

doi:10.1007/bf00205409

Cited by 51 publications

(20 citation statements)

References 61 publications

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“…The high lethality observed in tumor-bearing mice after injection of 10 pg of toxic endotoxin and 30 pg of MDP (Table 2) preparations, but that combined administration of MDP and detoxified endotoxin is far less toxic although it showed equal tumor-therapeutic activity. These data confirm and extend those of Ribi et al [12] that a direct relation between toxicity and therapeutic effectiveness is absent. Because Ribi et al [12] found that endotoxins from wild-type bacteria were not active in their system, they suggested that MDP would act as an adjuvant to antigen(s) exposed on endotoxin from rough-mutant bacteria but not on endotoxin from wild-type bacteria.…”

Section: Resultssupporting

confidence: 92%

“…These data confirm and extend those of Ribi et al [12] that a direct relation between toxicity and therapeutic effectiveness is absent. Because Ribi et al [12] found that endotoxins from wild-type bacteria were not active in their system, they suggested that MDP would act as an adjuvant to antigen(s) exposed on endotoxin from rough-mutant bacteria but not on endotoxin from wild-type bacteria. These antigen(s) would cross-react with tumor antigens.…”

Section: Resultssupporting

confidence: 92%

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Endotoxin-induced antitumor activity in the mouse is highly potentiated by muramyl dipeptide

Bloksma¹,

Hofhuis²,

Willers³

1984

Cancer Letters

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SUMMARYThe ability of aqueous solutions of various endotoxin preparations, mummy1 dipeptide (MDP) and combinations of endotoxin and MDP, to induce necrosis and regression of subcutaneous Meth A transplants in mice and their toxicity were studied. While intravenously injected toxic endotoxins, in contrast to a detoxified preparation and to MDP, induced considerable necrosis and regression of their own, addition of MDP potentiated the antitumor potential of both toxic and detoxified endotoxins to the same high degree. Detoxified endotoxin combined with MDP, however, was far less toxic than toxic preparations alone or combined with MDP. This indicates that toxicity isnot directly related to therapeutic potential.---

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Section: Resultssupporting

confidence: 92%

Section: Resultssupporting

confidence: 92%

Endotoxin-induced antitumor activity in the mouse is highly potentiated by muramyl dipeptide

Bloksma¹,

Hofhuis²,

Willers³

1984

Cancer Letters

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“…Past studies of reactivation of arthritis induced by intravenous injection of homologous or heterologous'25I-labeled PG-PS revealed that more PG-PS localizes to the joint previously injured by intraarticular injection of PG-APS than to the contralateral PBS-injected joint, presumably due in part to a prolonged increase in joint vascular permeability (7). A synergistic effect of LPS and muramyl dipeptide, the minimum essential peptidoglycan structure that possesses many of the activities of peptidoglycan (47), has been demonstrated in an in vivo model of antitumor activity (48) and in in vitro adjuvanticity assays (49). More recently, Galelli and Chedid (50) reported a remarkable synergistic effect of muramyl dipeptide and LPS on the induction of colony-stimulating activity in mice .…”

Section: Resultsmentioning

confidence: 96%

Lipopolysaccharide induces recurrence of arthritis in rat joints previously injured by peptidoglycan-polysaccharide.

Stimpson¹,

Esser²,

Carter³

et al. 1987

The Journal of Experimental Medicine

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LPS and peptidoglycan or covalent peptidoglycan-polysaccharide (PG-PS)' complexes are the major toxic components of bacterial cell walls. Lipid A and PG possess many of the biologic activities that LPS and PG-PS, respectively, have in common, such as pyrogenicity, polyclonal activation of lymphoid cells, complement activation, mitogenicity, macrophage activation, and adjuvanticity (1-3). Both also induce arthritis after injection into laboratory animals. Systemic injection of rats with a sterile, aqueous suspension of PG-PS from the group A streptococcus (PG-APS) induces a chronic erosive relapsing arthritis that has many features of rheumatoid arthritis (4-6). Distinct PG-PS structures from a number of other bacteria, including human indigenous intestinal species, induce arthritis of varying chronicity (7-10) . LPS induces primarily an acute arthritis of relatively short duration after intraarticular (i.a.) injection (7, 11-15), but there have been few reports of its arthropathic activity after systemic administration (16, 17, 17a) .In spite of the shared biologic properties and ubiquitous distribution of LPS and PG-PS, the interaction of their phlogistic activities in an inflammatory process has received little attention. During investigations of mechanisms of recurrent arthritis induced by PG-APS, we noted that a systemic injection of 100 Ag of Salmonella typhimurium LPS induced a transient recurrence of arthritis in rat joints previously inflamed by exposure to PG-APS (7,18) . We now report that the systemic injection of a much lower dose of LPS will induce a recurrence of arthritis injoints inflamed 3 wk previously by the intraarticular injection of PG-APS and describe this reaction in detail . We show that LPS from many bacteria, including Yersinia enterocolitica and Neisseria gonorrhoeae, are active ; that lipid A

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“…It was created in the 1970s by Edgar Ribi, a scientist at the US Rocky Mountain Laboratories, through systematic manipulation of the structure of LPS with acid and base hydrolysis in an effort to develop a detoxified form of ‘Coleys toxin’ [42,43] for cancer therapy [44]. In early tests, the anti-tumor activity of MPL appeared to be unimpaired relative to its parental LPS but with as little as 0.1% as much inflammatory toxicity.…”

Section: The Rise and Fall Of Mpl In The United Statesmentioning

confidence: 99%

No pain no gain? Adjuvant effects of alum and monophosphoryl lipid A in pertussis and HPV vaccines

Mitchell

Casella

2017

Current Opinion in Immunology

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Development of non-infectious subunit vaccines is hampered by a slow pipeline of new adjuvants to replace or enhance alum in part because expectations of safety are high. Transient vaccine side effects are not clinical priorities because they cause no lasting harm and vaccine development has appropriately been focused on avoidance of serious adverse events. As a result, surprisingly little is known about the extent to which side effects caused by a vaccines reactogencicity are predictive of successful immunization outcomes. Recent clinical studies of pertussis and human papillomavirus vaccines adjuvanted with alum or the TLR4 agonist monophosphoryl lipid A can be used to advance understanding of the relationship between vaccine side effects and immunization outcomes.

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Peptides as requirement for immunotherapy of the guinea-pig line-10 tumor with endotoxins

Cited by 51 publications

References 61 publications

Endotoxin-induced antitumor activity in the mouse is highly potentiated by muramyl dipeptide

Endotoxin-induced antitumor activity in the mouse is highly potentiated by muramyl dipeptide

Lipopolysaccharide induces recurrence of arthritis in rat joints previously injured by peptidoglycan-polysaccharide.

No pain no gain? Adjuvant effects of alum and monophosphoryl lipid A in pertussis and HPV vaccines

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