Monoclonal antibodies in cancer treatment: a review of recent progress.

Research advances and promising clinical outcomes with immunotherapeutics has led to a resurgence of incorporating monoclonal antibodies in cancer treatment. Unconjugated, conjugated and multi-target constructs are emerging as a conventional form of therapy along with the classical trio of surgery, radiation and chemotherapy. The recent major accomplishments in monoclonals include: first, the development of human and chimeric structures negating the induction of humoral responses to murine counterparts which limited use; second, protein engineering has improved the affinity and specificity of the antibody to its target; third, technics have been designed to select monoclonal antibodies imparting a biological consequence (function) following binding; and, lastly, recombinant proteins are being created with multiple epitopic specificities and/or fusion with other biologically active proteins such as toxins and cytokines/growth factors. Clinical efficacy in the treatment of haematological malignancies has secured a role for monoclonals in routine treatment. Evidence of clinical responses in patients with metastatic solid tumours is leading to the next generation of trials in the adjuvant setting. This paper presents an overview of the clinical experience with monoclonal antibodies in cancer treatment over the past 5 years. Our aim is to highlight the successes and advances, as well as noting limitations of antibody therapeutics. The advances seen support a continued effort to optimise the creation, selection and use of immunotherapeutics in the battle against cancer.

Purification and characterization of the human ovarian LH/hCG receptor and comparison of the properties of mammalian LH/hCG receptors.

Methods previously published by us [Wimalasena et al., J Biol Chem 260: 10689-10697, 1985; Wimalasena et al., J Biol Chem 261: 9416-9420, 1986] were utilized to solubilize the human corpus luteal leuteinizing hormone/human chorionic gonadotropin (LH/hCG) receptor with 3-[(3-cholamide-propyl)dimethylammonio]-1-propanesulfonate (CHAPS) and to purify the receptor by two steps of hCG-Sepharose affinity chromatography. The specific binding capacity (SBC) of the purified human receptor was 7510 pmol/mg protein, and KA = 2.2 x 10(9) M-1 when iodo hCG was competed by hCG; the yield was 4-7% of starting activity. When hLH was used in competition with hCG, specific binding capacity was 7900 pmol/mg protein and KA 1.0 x 10(9) M-1. Silver staining and autoradiography demonstrated a single protein of Mr 78,000 under reducing and Mr 58-62 x 10(3) under nonreducing conditions. Rat ovarian LH/hCG receptor was purified by similar methods and the KA of 3.5 x 10(10) M-1 for hCG was substantially different from the KA for hLH which was 2.1 x 10(9) M-1. Mr of the rat protein was 78-82 x 10(3) (reduced) and 58-62 x 10(3) (nonreduced) when analyzed by silver staining and autoradiography. For the first time, human LH/hCG receptor has been purified to apparent homogeneity, and its Mr of 78,000 was essentially identical to the Mr values of purified rat and porcine receptors.

Comparison of a latex agglutination test with five other methods for determining the presence of antibody against cytomegalovirus.

A latex agglutination test for determination of antibody against cytomegalovirus was compared with five other methods: a solid-phase fluorescent immunoassay, an indirect hemagglutination test, two solid-phase enzyme immunoassays, and an indirect fluorescent-antibody method, with sera collected from 210 random blood donors. Of the sera tested, 28% were positive for anti-cytomegalovirus by concordance of four or more methods. The latex agglutination test performed well, with a sensitivity of 100%, a specificity of 99%, and positive and negative predictive values of 97 and 100%, respectively. The methods were also evaluated for the number of sera requiring repeat testing, equivocal results after retesting, ease of performance, turnaround time, and technical demands. The tests which best met the requirements for a screening test were the solid-phase fluorescent immunoassay, the indirect hemagglutination test, and the latex agglutination test. The latex agglutination test is a valuable screening tool for detecting total anti-cytomegalovirus which has high sensitivity, high negative predictive value, and rare equivocal results and also has the added advantages of ease of performance and rapid turnaround time.