Response of refractory Hodgkin's disease to monoclonal anti-CD30 immunotoxin

Falini, Brunangelo; Flenghi, Leonardo; Aversa, Franco; Barbabietola, G; Martelli, MF; Comeli, P; Tazzari, Pier Luigi; Broe, Marianne Kjærvig; Stein, Harald; Dürkop, Horst; Pizzolo, Giovanni; Bolognesi, Andrea; Stirpe, Fiorenzo; Sabattini, Elena; Pileri, Stefano

doi:10.1016/0140-6736(92)91135-u

Cited by 198 publications

(94 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several Saporin-based immunotoxins have been developed. Anti-CD-30 (BER-H2/SO6) has been given to four patients with advanced refractory Hodgkin's disease (Falini et al, 1992). In three, there was a rapid and substantial reduction in tumor mass (50 to >75%); however, clinical responses were transient.…”

Section: Immunotoxinsmentioning

confidence: 99%

Novel antibodies as anticancer agents

2007

View full text Add to dashboard Cite

In recent years antibodies, whether generated by traditional hybridoma technology or by recombinant DNA strategies, have evolved from Paul Ehrlich's 'magic bullets' to a modern age 'guided missile'. In the recent years of immunologic research, we are witnessing development in the fields of antigen screening and protein engineering in order to create specific anticancer remedies. The developments in the field of recombinant DNA, protein engineering and cancer biology have let us gain insight into many cancer-related mechanisms. Moreover, novel techniques have facilitated tools allowing unique distinction between malignantly transformed cells, and regular ones. This understanding has paved the way for the rational design of a new age of pharmaceuticals: monoclonal antibodies and their fragments. Antibodies can select antigens on both a specific and a high-affinity account, and further implementation of these qualities is used to target cancer cells by specifically identifying exogenous antigens of cancer cell populations. The structure of the antibody provides plasticity resonating from its functional sites. This review will screen some of the many novel antibodies and antibody-based approaches that are being currently developed for clinical applications as the new generation of anticancer agents.

show abstract

Section: Immunotoxinsmentioning

confidence: 99%

Novel antibodies as anticancer agents

2007

View full text Add to dashboard Cite

show abstract

“…For in vivo therapy, the linkage between the antigen-binding molecule and the toxin must be sufficiently stable to remain intact until the immunotoxin reaches its target cells and then the toxin must be released. A saporin-containing immunotoxin, prepared as described here, has been used previously in a clinical trial for the treatment of refractory Hodgkin's disease and proved to be very promising (Falini et al, 1992 (Baselga et al, 1993). The conditions of treatment for in vivo experiments were fixed in order to achieve the maximum effect of immunoconjugates against a high number of grafted tumour cells.…”

Section: Discussionmentioning

confidence: 99%

Immunoconjugates made of an anti-EGF receptor monoclonal antibody and type 1 ribosome-inactivating proteins from Saponaria ocymoides or Vaccaria pyramidata

Massimo

Loreto²,

Pacilli³

et al. 1997

Br J Cancer

Self Cite

View full text Add to dashboard Cite

Summary The present paper describes two immunoconjugates consisting of an anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MAb), named Mint5, covalently linked to the type 1 ribosome-inactivating proteins (RlPs) ocymoidine (Ocy) and pyramidatine (Pyra) from Saponaria ocymoides and Vaccaria pyramidata respectively. Both antibody and toxins are shown to retain their respective biological properties upon chemical conjugation. The immunoconjugates exert specific inhibition of EGFR expressing target cell proliferation and protein synthesis in in vitro assays and also inhibit the growth of grafted human tumour cells in nude mice.Keywords: immunoconjugate; anti-epidermal growth factor receptor; ocymoidine; pyramidatineThe clinical use of immunotoxins for the treatment of cancer is currently under evaluation worldwide. The therapeutic potentiality of immunotoxins and preclinical and clinical results over the last 20 years have been reviewed recently (Thrush et al, 1996), indicating that, although immunotoxins seem promising for systemic therapy of haematological malignancies, a number of different problems still need to be solved, especially for the treatment of solid tumours. In particular, the refining of dose regimen and administration route, the combination with chemotherapy and the reduction of immunogenicity are the major goals of future research. In this paper, we describe the preparation of two new immunoconjugates made of an anti-epidermal growth factor receptor monoclonal antibody, named MintS, chemically linked to either ocymoidine or pyramidatine, toxins from Saponaria ocymoides and Vaccaria pyramidata respectively.The epidermal growth factor (EGF) and its receptor play a critical role in the growth and regulation of many normal and malignant cell types. EGFR overexpression is a common feature in most carcinomas and correlates with poor prognosis (Fox et al, 1994).The potential value of EGFR as a target for the diagnosis and therapy of human tumours has been recognized for several years, and the use of anti-EGFR monoclonal antibodies may provide therapeutic tools in the treatment of tumours overexpressing the receptor (Ennis et al, 1991).Moreover, immunoconjugates of EGFR-specific monoclonal antibodies to either gelonin (Ozawa et al, 1989) or ricin A chain (Masui et al, 1989) were shown to reduce the growth of human tumour cells transplanted into athymic mice.

show abstract

“…Antibodies directed against CD30 have been in clinical trials for years [48] and continue to be investigated in phase I or II trials (Table 1). A wide array of compounds has been developed and tested, largely in cell lines and murine models.…”

Section: Targeting Cd30mentioning

confidence: 99%

“…Most of the data are preclinical, with a few of the drugs having entered clinical trials. Clinical experience with anti-CD30 conjugated to saporin (a ribosome-inactivating protein) is summarized in Table 1 [48,71]. As a more recent example, SGN-35, a chimeric anti-CD30 antibody (SGN-30) conjugated to a new anti-mitotic agent, demonstrated potent cytotoxicity in CD30+ tumor cell lines and resulted in tumor regressions in murine xenograft models [72,73].…”

Section: Anti-cd30 Immunoconjugatesmentioning

confidence: 99%