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 bonemarrow 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.
ASJC Scopus subject areas
- Cancer Research