Herceptin-directed nanoparticles activated by an alternating magnetic field selectively kill HER-2 positive human breast cells in vitro via hyperthermia.

Purpose: HER-2 is in the EGF tyrosine kinase receptor family, overexpressed by many human cancers and minimally expressed by normal adult tissues. HER-2 expression in human cancers is correlated with reduced survival, increased metastasis, reduced apoptosis and increased proliferation. Herceptin is a humanised mouse antibody that targets and inactivates HER-2.

Rituximab-mediated cell signaling and chemo/immuno-sensitization of drug-resistant B-NHL is independent of its Fc functions.

Purpose: Rituximab [chimeric anti-CD20 monoclonal antibody], alone or combined with chemotherapy, is used in the treatment of non-Hodgkin's lymphoma (NHL). Rituximab binds to CD20 and inhibits intracellular survival/growth pathways leading to chemo/immunosensitization of tumor cells in vitro. The contribution of rituximab Fc-FcR interaction in signaling is not known.

Pharmacokinetics and tumor localization of (111)in-labeled HuCC49DeltaC(H)2 in BALB/c mice and athymic murine colon carcinoma xenograft.

The primary limitation of IgG antibodies for radioimmunotherapy of solid tumors is their prolonged serum half-life, leading to dose-limiting bone marrow toxicity at doses providing inadequate radiation to the tumor. A humanized C(H)2 domain-deleted variant of the anti-TAG-72 antibody CC49 (HuCC49DeltaC(H)2) has faster blood clearance, compared to the IgG, while retaining tumor targeting. We compared the pharmacokinetics and tumor uptake of (111)In-HuCC49DeltaC(H)2 in BALB/c mice and a colon carcinoma (LS-174T) mouse xenograft with that of (111)In-labeled chimeric CC49 (cCC49), an antibody with pharmacokinetics similar to the humanized CC49 parent.

Antibody therapy of non-Hodgkin's B-cell lymphoma.

Engineering antibodies with reduced immunogenicity and enhanced effector functions, and selecting antigen targets with the appropriate specificity, density, and/or functionality, have contributed to the recent clinical successes in using unconjugated "naked" antibody therapies of B-cell lymphoma (rituximab) and breast carcinoma (Herceptin). The non-overlapping toxicities of naked antibodies and chemotherapy, together with their potential synergy, which is based on unique and complementary mechanisms of action, have contributed to the creation of new standards of care in cancer therapy and management. Clinical trial results supporting these concepts are presented.