Lipid A and Immunotherapy

Ribi, Edgar; Cantrell, John L.; Takayama, K.; Qureshi, Nilofer; Peterson, John; Ribi, Hans O.

doi:10.1093/clinids/6.4.567

Cited by 114 publications

(61 citation statements)

References 22 publications

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“…75,76 Another TLR agonist of interest is monophosphoryl lipid (MPL) A, which targets TLR-4. 77 MPL is a derivate of LPS and induces a Th1-like cytokine response similar to LPS. 78 L-BLP25 (Stimuvax ® ) is a liposomal vaccine that incorporates MPL and carries TAAs targeting the extracellular core protein of MUC-1.…”

Section: Toll-like Receptor Agonistsmentioning

confidence: 99%

Enhancing immune responses to tumor-associated antigens

Higgins¹,

Bernstein²,

Hodge³

2009

Cancer Biology & Therapy

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The goal of vaccine-based cancer immunotherapy is to induce a tumor-specific immune response that ultimately reduces tumor burden. However, the immune system is often tolerant to antigens presented by the tumor, as the cancer originates from within a patient and is therefore recognized as self. This article reviews selected clinical strategies for overcoming this immune tolerance, and approaches to enhance generation of immunity to tumor-associated antigens by activating innate immunity, potentiating adaptive immunity, reducing immunosuppression, and enhancing tumor immunogenicity. Success in the field of cancer vaccines has yet to be fully realized, but intelligent choice of immunomodulators, tumor antigens and patient populations will likely lead to clinically relevant uses for cancer vaccines.

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Section: Toll-like Receptor Agonistsmentioning

confidence: 99%

Enhancing immune responses to tumor-associated antigens

Higgins¹,

Bernstein²,

Hodge³

2009

Cancer Biology & Therapy

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“…A successful approach to a formulation of lipid A with considerably reduced toxicity and retention of adjuvanticity was accomplished by Ribi and coworkers (120,121). LPS initially was extracted from cell walls obtained from the rough (Re) mutants of Salmonella species.…”

Section: Mplmentioning

confidence: 99%

“…In this regard, MPL together with trehalose dimycolate has been shown to cause regression of experimental VOL. 7,1994 tumors in several species (121). In order to exploit this potentially ther,apeutic adjuvant, Mitchell et al (102) incorporated MPL together with the cell wall skeleton of Mycobacterium phlei (analogous to trehalose dimycolate) in a squalene water-in-oil emulsion as an adjuvant to autologous melanoma antigens for immunization of humans.…”

Section: Mplmentioning

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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“…The immune potential of porin was found to be enhanced by LPS [4,10], and monoclonal antibodies (MoAbs), which recognized epitopes present in porin-LPS complexes, showed that these epitopes were protective against endotoxaemia and mouse typhoid [11]. However, the use of LPS as an immunological adjuvant is precluded by the fact that it is extremely toxic and pyrogenic for most animal species [12]. Recently, water soluble, nontoxic and synthetic polyelectrolytes were found to be efficient immunomodulators [13].…”

Section: Introductionmentioning

confidence: 99%

Influence of Immunopotentiators on the Antiporin Immunoglobulin G Subclass: Distribution and Protective Immunity Against Murine Salmonellosis

Nandakumar

Muthukkaruppan

1999

Scand J Immunol

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To improve the immune potential of porin (a pore‐forming protein of Salmonella sp.), different immunopotentiators such as Freund's complete adjuvant (FCA), lipopolysaccharide (LPS) and polyoxydonium (PO) were evaluated by studying the nature of the protective immune response induced against murine Salmonellosis. The nontoxic, synthetic heteropolymer polyoxydonium was as good as LPS at inducing antiporin immunoglobulin G (IgG) antibodies and protective immunity. Analysis of the antiporin IgG subclass pattern revealed a preferential increase in a particular subclass based on the immunopotentiator used. Porin, alone or emulsified in FCA, elicited predominantly antiporin IgG1 antibodies, whereas LPS preferentially evoked antiporin IgG2a, IgG2b and IgG3 antibodies. Polyoxydonium induced a clear shift towards antiporin IgG2b antibodies. The significance of these antiporin IgG subclass antibodies in protection against murine Salmonellosis was studied by passive immunization and by analysing the infected mouse sera.

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Lipid A and Immunotherapy

Cited by 114 publications

References 22 publications

Enhancing immune responses to tumor-associated antigens

Enhancing immune responses to tumor-associated antigens

Molecular adjuvants and immunomodulators: new approaches to immunization

Influence of Immunopotentiators on the Antiporin Immunoglobulin G Subclass: Distribution and Protective Immunity Against Murine Salmonellosis

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