Effects of Monoclonal Antibody Combined with Ganciclovir or &lt;i&gt;(S&lt;/i&gt;&lt;i&gt;)&lt;/i&gt;-1-[3-Hydroxy-(2-phosphonylmethoxy)-propyl]cytosine against Murine Cytomegalovirus Infections in Cell Culture and in Severe Combined Immunodeficient Mice

Smee, Donald F.; Sugiyama, S. T.; Sidwell, Robert W.; Barnett, Bill B.

doi:10.1159/000239335

Cited by 6 publications

(4 citation statements)

References 16 publications

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“…In these animal studies none of the interactions were antagonistic. We have used these synergy determination methods in other published works [21,22].…”

Section: Synergy Determinationsmentioning

confidence: 99%

Combination Treatment of Influenza A Virus Infections in Cell Culture and in Mice with the Cyclopentane Neuraminidase Inhibitor RWJ-270201 and Ribavirin

Smee

Bailey²,

Morrison³

et al. 2002

Chemotherapy

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Treatment of virus infections with compounds acting by different mechanisms may lead to more potent effects when these agents are used in combination. Under this premise, two known active influenza virus inhibitors, ribavirin and the novel cyclopentane influenza virus neuraminidase inhibitor (1S,2S,3R,4R)-3-[(1S)-(acetylamino)-2-ethylbutyl]-4-[(aminoiminomethyl)amino]-2-hydroxy-cyclopentanecarboxylic acid (RWJ-270201, BCX-1812) were studied. Experiments in cell culture demonstrated that RWJ-270201 plus ribavirin synergistically reduced extracellular influenza A/NWS/33 (H1N1) virus yields at low concentrations of each inhibitor. Mice were treated with ribavirin at 20 and 6.25 mg/kg/day combined with RWJ-270201 at 1, 0.32, or 0.1 mg/kg/day, or used alone. Treatments were twice daily for 5 days starting 4 h before exposure to influenza A/NWS virus. Only RWJ-270201 alone at 1 mg/kg/day significantly prevented mortality. In contrast, most drug combinations increased survival significantly compared to the placebo group. Doses of the two compounds used in combination delayed the mean day of death, and improved arterial oxygen saturation levels, as measured on day 11 of the infection. The combination of the two inhibitors produced additive to synergistic interactions in these mouse experiments with no enhancement of host toxicity. Treatment of influenza infections in the clinical setting may benefit by these two agents in combination.

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“…In these animal studies none of the interactions were antagonistic. We have used these synergy determination methods in other published works [21,22].…”

Section: Synergy Determinationsmentioning

confidence: 99%

Combination Treatment of Influenza A Virus Infections in Cell Culture and in Mice with the Cyclopentane Neuraminidase Inhibitor RWJ-270201 and Ribavirin

Smee

Bailey²,

Morrison³

et al. 2002

Chemotherapy

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“…122 CMV infection can result in retinitis and gastroenteritis in HIV-infected patients and may also cause chronic intrauterine infection. 122,123 Up to 40,000 cases of congenital CMV infection are reported each year; mental retardation and hearing loss may occur in about 25% of these cases. 122 Currently, there is no vaccine against CMV.…”

Section: Use Of Mabs In Therapy Against Complications Of Viral Infectmentioning

confidence: 99%

“…However, antibody ad-ministered along with ganciclovir in severe combined immunodeficient mice also produced only an additive effect. 123 The extent to which a MAb can protect the host from CMV infection cannot reliably be predicted from its immunoreactivity, neutralizing titers in vitro, or from its antigen-binding data, because the mechanism of action of a MAb in vitro and in vivo may be entirely different. 124 If an antibody is used along with drugs, not only is the treatment efficacy improved but also the side effects of a high drug concentration may be avoided.…”

Section: Use Of Mabs In Therapy Against Complications Of Viral Infectmentioning

confidence: 99%

Therapeutic Applications of Monoclonal Antibodies

Berger

Shankar

Vafai

2002

The American Journal of the Medical Sciences

148

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Researchers have sought therapeutic applications for monoclonal antibodies since their development in 1975. However, murine-derived monoclonal antibodies may cause an immunogenic response in human patients, reducing their therapeutic efficacy. Chimeric and humanized antibodies have been developed that are less likely to provoke an immune reaction in human patients than are murine-derived antibodies. Antibody fragments, bispecific antibodies, and antibodies produced through the use of phage display systems and genetically modified plants and animals may aid researchers in developing new uses for monoclonal antibodies in the treatment of disease. Monoclonal antibodies may have a number of promising potential therapeutic applications in the treatment of asthma, autoimmune diseases, cancer, poisoning, septicemia, substance abuse, viral infections, and other diseases.

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“…Monoclonal antibody D5.F10.B8 neutralizes MCMV (SN 50 , 7 g/ml), while monoclonal antibody C34.18.F6 does not. The derivation and the neutralizing activities of these monoclonal antibodies were described previously (19). Deglycosylated ricin A chain (Inland Laboratories, Inc., DeSoto, Tex.)…”

mentioning

confidence: 99%

Selective cytotoxicity of ricin A chain immunotoxins towards murine cytomegalovirus-infected cells

Barnett

Smee

Malek

et al. 1996

Antimicrob Agents Chemother

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Immunotoxins were constructed by linking immunoglobulins specific for murine cytomegalovirus (MCMV) to deglycosylated ricin A chain. Toxicities toward MCMV-infected and uninfected cells were determined by measuring the inhibition of protein synthesis following a 48-h exposure to immunotoxins commencing 24 h after infection. The 50% inhibitory concentrations ranged from 0.4 to 4 micrograms/ml for infected cells and from 22 to 120 micrograms/ml for uninfected cells. Selectivity indices ranged from 30 to 157. Control immunotoxins, which were constructed identically except that the immunoglobulin moiety had no specificity toward MCMV antigens, had 50% inhibitory concentrations of 50 and 100 micrograms/ml toward infected and uninfected cells, respectively.

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Effects of Monoclonal Antibody Combined with Ganciclovir or <i>(S</i><i>)</i>-1-[3-Hydroxy-(2-phosphonylmethoxy)-propyl]cytosine against Murine Cytomegalovirus Infections in Cell Culture and in Severe Combined Immunodeficient Mice

Cited by 6 publications

References 16 publications

Combination Treatment of Influenza A Virus Infections in Cell Culture and in Mice with the Cyclopentane Neuraminidase Inhibitor RWJ-270201 and Ribavirin

Combination Treatment of Influenza A Virus Infections in Cell Culture and in Mice with the Cyclopentane Neuraminidase Inhibitor RWJ-270201 and Ribavirin

Therapeutic Applications of Monoclonal Antibodies

Selective cytotoxicity of ricin A chain immunotoxins towards murine cytomegalovirus-infected cells

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