Humoral immune response to a ricin A chain immunotoxin in patients with metastatic melanoma

A. A. Herlter, L. E. Spitler, A. E. Frankel

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Immunotoxins, hybrid molecules consisting of a monoclonal antibody linked to a polypeptide toxin have shown anti-tumor activity in both animal models and early clinical trials. However, their potential value in the treatment of human cancer may be limited by the development of host antibodies against the conjugate. Such antibodies could potentially alter immunotoxin pharmacokinetics and pharmacodynamics as well as precipitate serum sickness and anaphylaxis. Using a radioimmunoassay we have measured serial anti-ricin A chain (anti-RTA) and anti-murine immunoglobulin (anti-MIG) titers in 22 patients who received the anti-melanoma immunotoxin XomaZyme®-Mel. Significant titers of anti-RTA and/or anti-MIG were detected in 17 of 21 evaluable patients. Of the four patients not developing antibodies, two were likely immunosuppressed secondary to dexamethasone, and CCNU and dexamethasone respectively. Both patients who received immunotoxin at a time when they had detectable anti-immunotoxin antibodies experienced infusion reactions consistent with immune mediated allergic responses. There was a decrease in peak immunotoxin level in the one patient who had serum immunotoxin levels measured at a time when anti-RTA was present. Strategies to suppress the human immune response to immunotoxins are required before repetitive courses of immunotoxin of this design may be administered.

Original languageEnglish (US)
Pages (from-to)245-253
Number of pages9
JournalCancer Drug Delivery
Volume4
Issue number4
StatePublished - 1987

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Ricin
Immunotoxins
Humoral Immunity
Melanoma
Dexamethasone
Antibodies
Immunoglobulins
Serum Sickness
Lomustine
Anaphylaxis
Radioimmunoassay
Anti-Idiotypic Antibodies
Neoplasms
Animal Models
Pharmacokinetics
Monoclonal Antibodies
Clinical Trials
Peptides

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology

Cite this

Humoral immune response to a ricin A chain immunotoxin in patients with metastatic melanoma. / Herlter, A. A.; Spitler, L. E.; Frankel, A. E.

In: Cancer Drug Delivery, Vol. 4, No. 4, 1987, p. 245-253.

Research output: Contribution to journalArticle

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