M. Gerretsen et al., THE FEASIBILITY OF RADIOIMMUNOTHERAPY OF HEAD AND NECK-CANCER, European journal of cancer. Part B, Oral oncology, 30B(2), 1994, pp. 82-87
Since the introduction of the hybridoma technology by Kohler and Milst
ein (Nature 1975, 256, 495-497), tremendous effort has been put in the
realisation of Ehrlich's concept of the magic bullet, which was propo
sed as early as the beginning of the century. The first clinical studi
es for radioimmunoscintigraphy (RIS) and radioimmunotherapy (RIT) with
radiolabelled antibodies were undertaken in the early 1980s. Since th
en, RIS has been performed on thousands of patients with various types
of malignancies, like colon carcinoma, lung carcinoma, breast carcino
ma, neuroblastoma, T-cell lymphoma and ovarian carcinoma. In addition,
a substantial number of therapy trials with radiolabelled antibodies
have been performed. The developments for head and neck squamous cell
carcinoma (HNSCC) have only recently been able to catch up with these
events to some extent. One of the main reasons for this slow progress
has been the lack of monoclonal antibodies (Mab) with specificity for
HNSCC. Although there are as yet no real tumour specific antigens know
n for HNSCC, which also holds true for the majority of malignancies ar
ising from other tissues, we now have the availability of a number of
Mab with high specificity for HNSCC and with a very restricted reactio
n pattern with normal tissues. Labelled with I-131, these Mab have bee
n shown to be highly capable to localise in HNSCC xenografts in nude m
ice. Based on these promising data, patient studies with one of these
Mab, designated Mab E48, labelled with Tc-99m, were started to evaluat
e the feasibility of RIS in patients with head and neck cancer. The fi
rst results of these studies indicated the capacity of Tc-99m-labelled
Mab E48 F(ab')(2) as well as IgG to detect metastatic and recurrent d
isease in these patients. These data justified further studies investi
gating the possibilities for RIT with this Mab. In preclinical experim
ents, the capacity of (131m)-labelled Mab E48 IgG to eradicate establi
shed HNSCC tumours in nude mice was shown. Following the latest develo
pments in the field of radioimmunoconjugate chemistry and anticipating
the need for more appropriate radionuclides for clinical applications
, a technical protocol for the labelling of Mab with Re-186 was develo
ped. Labelled with Re-186, Mab E48 appears to be even better suited to
eradicate established tumours than when labelled with I-131. Based on
these encouraging observations we are now making preparations for the
first RIT studies with Re-186-labelled Mab E48 in patients with head
and neck cancer.