Monoclonal antibody therapy of malignant melanoma: in vivo localization in cutaneous metastasis after intravenous administration.

Abstract

The murine antimelanoma monoclonal antibody, 9.2.27, was administered intravenously to eight patients with metastatic malignant melanoma. Biopsies of metastatic nodules clearly demonstrate the selective localization of this antibody on the melanoma cell surface with a dose-response relationship to the quantity of administered antibody. The antibody infusions were clinically well tolerated and the pharmacokinetics of the antibody and the antiglobulin responses are described. This study indicates that murine monoclonal antibodies have potential as selective targeting agents in the design of future therapeutic trials using monoclonal antibodies or conjugates thereof in the treatment of cancer.

Melanoma‐associated chondroitin sulphate proteoglycan as a new target antigen for CD4+ T cells in melanoma patients

“…[30][31][32] Furthermore, we could detect significant MCSP T cell reactivity in the blood of both, healthy donors and melanoma patients without any clinical signs of autoimmunity.…”

Pre-existing anti-mouse immunoglobulin in a patient receiving 131I-murine monoclonal antibody for radioimmunolocalisation

“…The in vivo handling of radiolabelled MCAs in patients with melanoma who developed an anti-mouse response following repeated injections is not so clear. Oldham et al (1984), reported unaltered pharmacokinetics but Larson et al (1983), using a different antimelanoma MCA, observed an increase in the rate of clearance from the circulation with an increase in liver uptake and a decrease in tumour uptake. An immune response in a sensitised individual to a radiolabelled MCA may result in its accelerated catabolism and dehalogenation, with rapid excretion of most of the unbound radionuclide within 24h (J. Kemshead unpublished observation).…”

“…These immune responses have been reported in 50% of patients with melanoma that were given repeatedly large doses of a MCA. These responses consisted of both IgG and IgM (Oldham et al, 1984). There are few reports in the literature concerning the presence of pre-existing anti-mouse activity in…”

“…Of more importance, however, would be the consequence of administering a large quantity of animal antibody to an individual possessing pre-existing anti-species immunoglobulin, as might occur in attempted therapy. This might result in serum sickness in such a susceptible patient (Oldham et al, 1984), together with altered pharmacokinetics of potentially therapeutic conjugates.…”

“…Pre-existing anti-mouse immunoglobulin in a patient receiving 1311-murine monoclonal antibody for radioimmunolocalisation A.G Radiolabelled monoclonal antibodies (MCAs) which recognise tumour-associated antigens are being used increasingly for radioimmunolocalisation (RIL) and trials of treatment for various malignancies, (Miller et al, 1982(Miller et al, , 1983Foon et al, 1984;Dillman & Royston, 1984). The majority of these MCAs are murine.…”