Minimal toxicity during protein a immunoadsorption treatment of malignant disease: An outpatient therapy

Abstract

Extracorporeal removal or modulation of circulating immune complexes (CIC) from plasma of animals and humans with malignant disease may be associated with induction of immune-mediated anti-tumor responses. Immunoadsorption columns containing heat-killed and formalin-fixed Staphylococcus aureus or staphylococcal protein A have been used for this purpose but treatments have often been associated with cardiopulmonary toxicity. Recently, an immunoadsorption device containing highly purified protein A covalently attached to a silica matrix (PROSORBA column) was used to treat 142 patients with refractory malignancies and 22 of 104 patients evaluated for anti-tumor response had objectively measurable reduction in tumor burden. In contrast to earlier experience with other devices, the procedures used in this trial were well tolerated and could be performed on an outpatient basis. The most common side effects observed among 1,306 treatments were chills (28% of treatments), low grade fever (28%), and musculoskeletal pain (16%). Side effects were mild to moderate and required no treatment or only symptomatic treatment. Treatment schedules were interrupted due to side effects for only six patients and there were no treatment-related deaths. Of 64 patients available for long-term follow-up evaluation (mean of 11 months), none exhibited evidence of long-term treatment-related side effects. None of the patient deaths in that period were associated with short or long-term treatment-related side effects. Protein A-silica (PROSORBA columns) can be used safely for development of further experimental treatments of malignant disease.

Exosome removal as a therapeutic adjuvant in cancer

“…This plasma filtering device consists of highly purified protein A from Staphylococcus aureus covalently linked to a silica matrix to capture circulating immunoglobulin G (IgG) and immune complexes containing IgG, which was FDA-approved for rheumatoid arthritis and idiopathic thrombocytopenic purpura as a complementary therapy for clearing pathogenic autoantibodies. In a study examining the efficacy of the Prosorba column in cancer, there was a measurable reduction in tumor burden in 22 of 104 patients and increased immune system activity reportedly occurred in the hours following treatment [126,127]. However, in a Phase II trial of metastatic breast cancer, circulating immune complexes were not detected in the majority of patients and treatment with the Prosorba column did not confer clinical benefits [128].…”

Successful management of paraprotein‐associated peripheral polyneuropathies by immunoadsorption of plasma with staphylococcal protein A

“…Although generally well tolerated [28], and not complicated by the coagulopathy of plasma exchange [ 141, this therapy has been associated with severe and even life-threatening complications [30,3 I ] . When performed by the "off-line" technique, it can be more convenient and less traumatic to the patient, and potentially less expensive than conventional therapies.…”

The low-throughput protein A adsorber: an immune modulatory device. Hypothesis for the mechanism of action in the treatment of rheumatoid arthritis

“…13,33,38,44 Hypotension, abdominal pain, headache, diarrhea, respiratory symptoms, dizziness, weakness, and edema as well as hypersensitivity-type reactions have been reported in few patients. 13,38,42,45,46 Leukocytoclastic vasculitis of the skin is a rare involvement of the kidneys and is a very rare complication of immunoadsorption. Immune complexes in the glomeruli influence the course of the renal disease.…”

“…18 However, the data are controversial in this field. 41,42 Diverse effects of the scavenging system following Prosorba treatment of various diseases imply an immunomodulatory impact. 19 Side effects…”