Antigen-targeted liposome-encapsulated methotrexate specifically kills lymphocytes sensitized to the nonapeptide of myelin basic protein

Boggs, Joan M.; Goundalkar, Ashok; Doganoglu, F.; Samji, N.; Kurantsin‐Mills, Joseph; Koshy, Kalavelil M.

doi:10.1016/0165-5728(87)90029-4

Cited by 12 publications

(4 citation statements)

References 19 publications

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“…Binding of liposomes to specific target cells might allow the AMB to interact with the target cells and leave nontarget cells unaffected. We are interested in targeting drugs to antigen-specific clones of T lymphocytes (5). In preparation for this, we investigated the effect of Fungizone and untargeted liposomal AMB on the in vitro proliferation of T lymphocytes.…”

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confidence: 99%

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Liposomal amphotericin B inhibits in vitro T-lymphocyte response to antigen

Boggs

Chang

Goundalkar

1991

Antimicrob Agents Chemother

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The effects of free amphotericin B (as Fungizone) and amphotericin B (AMB) incorporated into liposomes on the proliferation of lymphocytes were determined. Freshly obtained guinea pig and rat antigen-specific lymphocytes were compared with rat T-lymphocyte cell lines cultured for a long period of time. Incorporation of AMB into multilayered vesicles significantly reduced its effect relative to that of Fungizone on cultured T-cell lines, as reported by others for mammalian cells. In contrast, the effects on freshly obtained antigen-specific lymphocytes were different. Fungizone inhibited proliferation of antigen-specific lymph node cells freshly obtained from immunized guinea pigs at fungicidal concentrations, and incorporation into multilayered lipid vesicles did not have much of a protective effect. Higher concentrations of Fungizone were required to inhibit proliferation of fresh rat lymph node cells, but incorporation into multilayered lipid vesicles still did not have much of a protective effect. Some T lymphocytes in the peripheral circulation of guinea pigs and in the lymph nodes of rats were more resistant to liposomal AMB than another more sensitive T-lymphocyte population was. Proliferation of lymphocytes in response to mitogens was inhibited less than that in response to specific antigen was. Thus, sensitivity to AMB depended on the species, the strength of the stimulus used to activate the lymphocytes, and on some other property of the lymphocytes, possibly their state of differentiation. Regardless of the reason for the difference in effects on freshly obtained lymph node lymphocytes and cultured line cells, the former may be more relevant to effects in vivo and should be considered in a complete evaluation of the in vivo toxicity of these forms of the drug. Incorporation into sonicated unilamellar vesicles had more of a protective effect, while equimolar drug-lipid complexes had even more of a protective effect. These forms of AMB might have less of an immunosuppressive potential than multilayered vesicles containing low amounts of AMB do.

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confidence: 99%

“…For Lewis rats, it also contained 25 mM HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid), buffer, 1 mM sodium pyruvate, 0.1 mM nonessential amino acids, and 1% rat serum instead of guinea pig serum. Peripheral blood lymphocytes (PBLs) were isolated from guinea pig blood as described previously (5).…”

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confidence: 99%

Liposomal amphotericin B inhibits in vitro T-lymphocyte response to antigen

Boggs

Chang

Goundalkar

1991

Antimicrob Agents Chemother

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“…At present, we favor the idea that a first recognition step between the peptide exposed at the surface of liposomes and antigen-specific membrane-bound antibodies at the surface of B cells, is followed by presentation of the antigen to T cells (with or without processing), the response being amplified by MPLA and factors secreted by the immunocompetent cells. The strategy of aiming lymphocytes in vivo with a peptide-targeted liposome has already been attempted, albeit with another aim,with some success [50].…”

Section: Discussionmentioning

confidence: 99%

Parameters affecting the immunogenicity of a liposome‐associated synthetic hexapeptide antigen

Frisch¹,

Muller²,

Briand³

et al. 1991

Eur J Immunol

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The effect of liposome association on the immunogenicity of the hexapeptide IRGERA was investigated. When administered in the absence of a carrier and adjuvant this peptide, which corresponds to a linear epitope located at the C-terminus of histone H3, was not immunogenic. When mice were immunized with the peptide covalently linked to the surface of small unilamellar vesicles containing monophosphoryl lipid A as adjuvant, a relatively long-lasting response with memory cell induction was observed. The anti-peptide antibodies raised in this way reacted with the cognate sequence in the native histone. In contrast, coupling of the peptide to the surface of large vesicles yielded both an IgM and IgG response of short duration whereas encapsulation of the free peptide in large vesicles was ineffective. These results indicate that with short synthetic peptides, liposomes provide a substitute for a carrier protein. However, an adjuvant has to be incorporated in the vesicles in order to obtain an efficient immune response. Such an approach may be useful for designing synthetic vaccines.

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“…Interestingly, most of the work concerning drug targeting to MS has been done using liposomes [28,[126][127][128][129][130][131][134][135][136][137], although there is no reason to assume that other types of drug delivery systems would be unsuitable for this purpose. Whereas there are several studies demonstrating the accumulation of liposomes in sites of active…”

Section: Drug Targeting In Multiple Sclerosismentioning

confidence: 99%