Preliminary Observations of the Effects on Breast Adenocarcinoma of Plasma Perfused over Immobilized Protein A

Terman, David S.; Young, James B.; Shearer, William T.; Ayus, Carlos; Lehane, Daniel E.; Mattioli, Carlos A.; Espada, Rafael; Howell, Jimmy F.; Yamamoto, Tsuyoshi; Zaleski, Henry I.; Miller, Lisa Karen; Frommer, Peter L.; Feldman, Louis; Henry, J. E.; Tillquist, Richard; Cook, Gary; Daskal, Yerach

doi:10.1056/nejm198111123052006

Cited by 124 publications

(20 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One of the assumptions of extracorporeal immunoadsorption treatment has been that it removes blocking factors (IC) and IgG from circulation [1,22,25,30,37,42]. Results of our studies showed that at least 72% of the material removed from plasma of melanoma patients after radioiodination was 78 or smaller.…”

Section: Discussionmentioning

confidence: 82%

“…We [26] treated four patients with melanoma by extracorporeal immunoadsorption using heat-killed and formalin-fixed Staphylococcus aureus Cowan I in an attempt to remove IgG and/or its immune complexes from the circulation [30,37]. A problem similar to that of the CIC studies existed in extracorporeal immunoadsorption studies with cancer patients, i.e., the immunologic nature of the IC removed by this treatment modality was unknown most of the time.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Nature of antigens and antibodies in immune complexes isolated by staphylococcal protein A from plasma of melanoma patients

Gupta

Leitch

Morton

1983

Cancer Immunol Immunother

View full text Add to dashboard Cite

Immune complexes (IC) were isolated from plasma of melanoma patients by absorption to staphylococcal protein A and subsequent elution with MgCl2. The isolated ICs were purified by precipitation with polyethylene glycol and sucrose density gradient ultracentrifugation after radioiodination with 125I. The purified ICs were dissociated and radiolabeled antigen/antibody components were separated by ultracentrifugation at low pH (2.6). Under these conditions, about 72% radioactivity of the purified IC remained in the light-density region as a wide band. After neutralization, 26%-60% radioactivity in the region of 5S sedimentation bound to immobilized autologous immunoglobulins, as opposed to a maximum of 23% to immobilized immunoglobulins from human normal serum. Significant levels (73%-77%) of radioactivity in 7S region bound to rabbit anti-human IgG immunobeads. Immunoprecipitation of the antigen fraction by allogeneic anti-melanoma and rabbit anti-melanoma antibodies followed by SDS-polyacrylamide gel electrophoresis revealed the presence of a fetal antigen (FA) and a melanoma tumor-associated antigen (TAA). In addition, the presence of auto-antigen(s) was indicated by using autologous antibody in immunoprecipitation. Immunoglobulins (IgG) isolated from purified IC bound to cultured melanoma, sarcoma, and normal fibroblasts, although the binding to sarcoma and normal fibroblasts could be inhibited by preincubation of isolated IgG with soluble FA but not with soluble melanoma TAA. Thus, results of this investigation provide evidence that circulating IC in melanoma patients are composed of at least IgG and different antigens, and some of these antigens are produced by their tumor.

show abstract

Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Nature of antigens and antibodies in immune complexes isolated by staphylococcal protein A from plasma of melanoma patients

Gupta

Leitch

Morton

1983

Cancer Immunol Immunother

View full text Add to dashboard Cite

show abstract

“…In contrast to initial experiences with tumor regression in protein-A-perfused animals [36][37][38][39], both tem porary (partial) remissions [13,16,34,40,44] and treatment failures [ 11,20] have been reported in patients with a variety of malig nancies. Species-related response differences to protein A perfusion may be of impor tance.…”

Section: Discussionmentioning

confidence: 93%

Ex vivo and in vivo Protein A Perfusion: Background, Basic Investigations, and First Clinical Experiences

Samtleben¹,

Schmidt²,

Gurland³

1987

Blood Purif

View full text Add to dashboard Cite

During the past several years clinical protein A perfusion has attracted much attention because it allows to selectively remove IgG subclasses 1, 2, 4 and probably IgG-containing immune complexes, and has a tumoricidal effect in experimental animals and in some cancer patients. Due to several drawbacks, this therapy is not yet generally accepted. Our first experience with laboratory and clinical protein A perfusions confirms several limitations of this new apheresis therapy. Plasma IgG extraction in the ex vivo system under investigation and during clinical application of protein A perfusion reached a 10:1 ratio of grams IgG removed per gram solid-phase protein A only in 2 of 5 runs. Nevertheless, the absolute amount of IgG removed was very low in all runs due to the restricted protein A load (maximum 200 mg) per column. Removal capacity can be increased by a two-column switchover system with subsequent perfusion and elution. Furthermore, the side effects observed in both in vivo treatments exceeded by far those of other extracorporeal therapies and had not been observed in more than 1,200 unselective plasma exchanges or in 50 cascade filtrations in our center. C3a generation in protein A perfusion is, however, comparable to cascade filtration, but exceeds that of unselective plasma exchange and is lower than in hemodialysis. Consequently, side effects in protein A perfusion cannot be correlated with the total amount of anaphylatoxin generated but may be due to a leakage of protein A or contaminants. Clinical application of protein A perfusion needs a more detailed elaboration in respect to biocompatibility, removal capacity, and the significance of the induced biological effects.

show abstract

“…Using these methods, an improvement in performance status, a reduction of tumor size and a positive conversion of the tuberculin reaction have been observed. Terman et al [19] reported a reduction in the tumor size of breast cancer after hemoper-fusion with protein A, which adsorbs the Fc fraction of IgG species. Recently, Rosenberg et al [8,15] demonstrated the therapeutic benefits of direct adoptive immunotherapy with LAK cells.…”

Section: Discussionmentioning

confidence: 99%

Induction of antitumor activities in spleen cells from mice and rats activated with lipopolysaccharide immobilized on beads

Abe

Tani

Shibata

et al. 1992

Cancer Immunol Immunother

View full text Add to dashboard Cite

Lipopolysaccharides (LPS) were coupled to polystyrene beads in order to apply the LPS without toxicity. The antitumor activity of the LPS-immobilizing beads was studied in experiments in vitro and in vivo. In vitro studies showed that spleen cells from C3H/HeN mice stimulated by beads immobilizing LPS from Escherichia coli produced cytolytic activity as strong as that of lymphokine-activated killer (LAK) cells. Spleen cells from Sprague-Dawley rats stimulated by beads immobilizing LPS from Salmonella minnesota produced cytolytic activity stronger than that of LAK cells. However, spleen cells stimulated by beads immobilizing each component of the LPS separately could not induce cytolysis. Contact stimulation, even for a brief period, sufficed for cytolytic activity, and was enhanced by culture for 48-72 h. Through in vivo studies, the suppression of tumor growth and a prolongation of the survival time were observed in tumor-bearing mice injected with spleen cells activated by beads immobilizing LPS from E. coli, and in mice injected with LAK cells. The effect of the activated spleen cells was stronger than that of the LAK cells. In rats bearing metastatic tumors, spleen cells activated by beads immobilizing LPS from S. minnesota suppressed lung metastases more strongly than did LAK cells. These findings indicate that LPS immobilized by beads induced killer cells more strongly than interleukin-2. Ex vivo immunomodulation with LPS-immobilizing beads can be applied usefully as an anticancer treatment.

show abstract

Preliminary Observations of the Effects on Breast Adenocarcinoma of Plasma Perfused over Immobilized Protein A

Cited by 124 publications

References 22 publications

Nature of antigens and antibodies in immune complexes isolated by staphylococcal protein A from plasma of melanoma patients

Nature of antigens and antibodies in immune complexes isolated by staphylococcal protein A from plasma of melanoma patients

Ex vivo and in vivo Protein A Perfusion: Background, Basic Investigations, and First Clinical Experiences

Induction of antitumor activities in spleen cells from mice and rats activated with lipopolysaccharide immobilized on beads

Contact Info

Product

Resources

About