An anti-CD5 immunotoxin for chronic lymphocytic leukemia: enhancement of cytotoxicity with human serum albumin-monensin

A. A. Hertler, D. M. Schlossman, M. J. Borowitz, H. E. Blythman, P. Casellas, A. E. Frankel

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Abstract

Five patients with B-cell chronic lymphocytic leukemia (B-CLL) were treated with 6 courses of the anti-CD5 immunotoxin T101-ricin A chain (T101-RTA). Each course consisted of 8 bi-weekly infusions of T101-RTA (7 or 14 mg/m2). The immunotoxin was well tolerated in all cases with no major toxicities. Though saturation of circulating leukemic cell-associated target antigen was demonstrated by FACS analysis in all patients, no intact immunotoxin was detected in bone-marrow or lymph-node aspirates. Pharmacokinetic studies revealed rapid clearance of T101-RTA, with a half-life of 43 min. None of the patients developed detectable titers of antibody against either T101 murine antibody or ricin A chain. Clinical response was limited to a rapid and transient fall in WBC count lasting less than 24 hr, most likely secondary to the antibody portion of the conjugate. In vitro, fresh B-CLL cells were resistant to T101-RTA at concentrations up to 10-8M, while fresh malignant T-cells with a 10-fold increase in expression of CD5 antigen were sensitive. In the presence of the enhancing agent human serum albumin-monensin, fresh B-CLL cells were sensitive to T101-RTA, with an ID50 more than 2 logs below the maximal concentration of immunotoxin achieved in vivo. We conclude that T101-RTA is a potentially useful agent in the treatment of T-cell leukemias. In the presence of HSA-monensin, this spectrum of activity may be extended to B-CLL.

Original languageEnglish (US)
Pages (from-to)215-219
Number of pages5
JournalInternational Journal of Cancer
Volume43
Issue number2
StatePublished - 1989

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Immunotoxins
Monensin
B-Cell Chronic Lymphocytic Leukemia
Serum Albumin
Ricin
Antibodies
CD5 Antigens
T-Cell Leukemia
Half-Life
Pharmacokinetics
Lymph Nodes
Bone Marrow
T-Lymphocytes
Antigens
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

An anti-CD5 immunotoxin for chronic lymphocytic leukemia : enhancement of cytotoxicity with human serum albumin-monensin. / Hertler, A. A.; Schlossman, D. M.; Borowitz, M. J.; Blythman, H. E.; Casellas, P.; Frankel, A. E.

In: International Journal of Cancer, Vol. 43, No. 2, 1989, p. 215-219.

Research output: Contribution to journalArticle

Hertler, A. A. ; Schlossman, D. M. ; Borowitz, M. J. ; Blythman, H. E. ; Casellas, P. ; Frankel, A. E. / An anti-CD5 immunotoxin for chronic lymphocytic leukemia : enhancement of cytotoxicity with human serum albumin-monensin. In: International Journal of Cancer. 1989 ; Vol. 43, No. 2. pp. 215-219.
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AU - Casellas, P.

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