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

Int J Cancer. 1989 Feb 15;43(2):215-9. doi: 10.1002/ijc.2910430207.


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(-8)M, 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.

MeSH terms

  • Aged
  • Antibodies / analysis
  • Antibodies / therapeutic use
  • Antigens, Differentiation / immunology*
  • CD5 Antigens
  • Drug Administration Schedule
  • Female
  • Humans
  • Immunotoxins / immunology
  • Immunotoxins / therapeutic use*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Leukemia, Lymphocytic, Chronic, B-Cell / therapy*
  • Male
  • Middle Aged
  • Ricin / immunology*


  • Antibodies
  • Antigens, Differentiation
  • CD5 Antigens
  • Immunotoxins
  • Ricin