Keyhole limpet hemocyanin immunotherapy of bladder cancer: laboratory and clinical studies.

Abstract

BACKGROUND:

Since the serendipitous observation by Olsson in 1974 that patients immunized with 5 mg of keyhole limpet hemocyanin (KLH) had a marked reduction in recurrence of superficial bladder cancer, multiple laboratory and clinical studies have confirmed the efficacy of KLH immunotherapy.

RESULTS:

In 1981, we reported that KLH immunotherapy reduced tumor growth and prolonged survival in the MBT-2 murine model of transitional cell carcinoma (TCC), and in 1988, Jurincic and co-workers demonstrated that KLH was superior to mitomycin C chemotherapy in preventing bladder tumor recurrence. Subsequent studies using Immucothel (Biosyn), crude KLH, and endotoxin-free KLH confirmed the efficacy of KLH immunotherapy in the MBT-2 murine bladder cancer model (p < 0.05), and resulted in up to 100% survival.

CONCLUSIONS:

To evaluate the efficacy of KLH immunotherapy in patients, a multicenter clinical trial was performed. Sixty-four patients with CIS or residual stage T(a), T(1) TCC, or both were enrolled in a phase I-II trial of escalating doses of weekly KLH given intravesically for 6 weeks. Patients were followed with cystoscopic examination, urine cytology, and bladder biopsy. Complete response was seen in 50% of patients with CIS, 20% of patients with residual T(a), T(1) TCC, and 33% of patients with both CIS and residual T(a), T(1) TCC. Responses occurred at all doses tested: 0.4, 2, 10 and 50 mg. No significant difference in response according to dose was noted, but optimal overall complete response was seen with a dose of only 2 mg. The toxicity of KLH is minimal. KLH appears to be a safe and highly effective immunotherapy for superficial bladder cancer.

• Authors: D L Lamm, J I Dehaven, D R Riggs
• Journal: European urology (Eur Urol) Vol. 37 Suppl 3 Pg. 41-4 ( 2000) ISSN: 0302-2838 [Print] Switzerland
• PMID: 10828686 (Publication Type: Clinical Trial, Journal Article, Multicenter Study)
• Copyright: Copyright 2000 S. Karger AG, Basel

Chemical References

• Adjuvants, Immunologic
• Hemocyanins
• keyhole-limpet hemocyanin

Topics

• Adjuvants, Immunologic (therapeutic use)
• Animals
• Carcinoma, Transitional Cell (drug therapy)
• Hemocyanins (therapeutic use)
• Humans
• Mice
• Urinary Bladder Neoplasms (drug therapy)