Keyhole limpet haemocyanin in experimental bladder cancer

Citation
Jf. Linn et al., Keyhole limpet haemocyanin in experimental bladder cancer, EUR UROL, 37, 2000, pp. 34-40
Citations number
35
Categorie Soggetti
Urology & Nephrology
Journal title
EUROPEAN UROLOGY
ISSN journal
03022838 → ACNP
Volume
37
Year of publication
2000
Supplement
3
Pages
34 - 40
Database
ISI
SICI code
0302-2838(2000)37:<34:KLHIEB>2.0.ZU;2-7
Abstract
Objectives: Keyhole limpet haemocyanin (KLH) is a high-molecular-weight pro tein antigen collected from the haemolymph of the sea mollusk Megathura cre nulata. it is a powerful non-specific immune response modifier that induces both a cell-mediated and a humoral response in animals and man. Thus, it i s commonly used clinically as a measure of immune competence. In 1974, Olso n studied the immune competence of bladder cancer patients by intradermal a pplication of KLH. He later observed a significant reduction of recurrent d isease in this patient group compared to another not immunized with KLH. Th is prompted a variety of experimental and clinical studies using KLH as an immunotherapy for recurrent bladder cancer. Methods: Three different bladde r cancer models have been used for experimental studies: intravesical trans plantation of tumour cells in syngeneic mouse bladders; subcutaneous transp lantation of tumour cells in syngeneic mice; direct chemical induction of b ladder tumours by feeding rats with the carcinogen N-butyl-N-(4-hydroxybuty l)nitrosamine. Results: The efficacy of KLH as an immunotherapeutic agent h as been compared with different immune response modifiers alone or in combi nation with these in 11 experimental studies. Mast of the studies used diff erent concentration and application schedules for KLH. In addition a pre-im munisation prior to inoculation of the tumour was not performed in all stud ies. Therefore it is not useful to compare the results of these studies. Ho wever, most of the experiments demonstrated a significant effect on tumour appearance and extension after treatment with KLH. Intralesional or systemi c application of KLH seemed to be superior to intravesical treatment. Pre-i mmunisation with KLH several days or weeks before tumour inoculation also s eems to be a key point of success. No study reported severe side-effects af ter application of KLH; additionally performed toxicity studies underlined the good tolerability of KLH. Conclusion: Based on all the experimental stu dies, KLH has to be judged as an effective and safe immunotherapeutic drug for the treatment of experimental bladder cancer. Prospective randomised cl inical trials should evaluate the role of KLH as an immunotherapeutic alter native in the prophylaxis of recurrent bladder cancer and should determine whether the efficacy of KLH in man may be improved by systemic application. Copyright (C) 2000 S. Karger AG, Basel.