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.