Keyhole limpet hemocyanin immunotherapy of bladder cancer: laboratory and clinical studies.
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.
Lamm
D L
DL
Department of Urology, Robert C. Byrd Health Science Center, West Virginia University, Morgantown 26506-9251, USA. Dlamm@hsc.wvu.edu
Dehaven
J I
JI
Riggs
D R
DR
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D006433:Hemocyanins / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
D000276:Adjuvants, Immunologic; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin