Today there are many licensed antiviral drugs, but the emergence of drug resistant strains sometimes invalidates the effects of the current therapies used in the treatment of infectious diseases. Compared to conventional antiviral drugs, monoclonal antibodies (mAbs) used as pharmacological molecules have particular physical characteristics and modes of action, and, therefore, they should be considered as a distinct therapeutic class. Despite being historically validated, antibodies may represent a novel tool for combatting infectious diseases. The current high cost of mAbs' production, storage and administration (by injection only) and the consequent obstacles to development are outweighed by mAbs' clinical advantages. These are related to a low toxicity combined with high specificity and versatility, which allows a specific antibody to mediate various biological effects, ranging from the virus neutralization mechanisms to the modulation of immune responses.This review briefly summarizes the recent technological advances in the field of immunoglobulin research, and the current status of mAb-based drugs in clinical trials for HIV and HCV diseases. For each clinical trial the available data are reported and the emerging conceptual problems of the employed mAbs are highlighted.This overview helps to give a clear picture of the efficacy and challenges of the mAbs in the field of these two infectious diseases which have such a global impact.

The data herein reported show that NBDHEX mediates efficient killing of both MDR1-Pgp and MRP1 over-expressing AML cells. Therefore, this drug can potentially be used as an effective agent for treating MDR in AML patients.

Background: CEA is a tumor-associated antigen abundantly expressed on several cancer types, including those naturally refractory to chemotherapy. The selection and characterization of human anti-CEA single-chain antibody fragments (scFv) is a first step toward the construction of new anticancer monoclonal antibodies designed for optimal blood clearance and tumor penetration.

Despite biotechnological and clinical applications very few monoclonal antibodies (MAbs) directed to the enzyme glucose oxidase, have been produced so far because of the heavy side effects of the immunization schedule for conventional MAb preparation. In contrast, the phage display method allows for the selection of monoclonal human antibody fragments against any antigens, including toxic proteins. Furthermore, cDNA sequences encoding selected antibody fragments are readily identified, facilitating various molecular targeting approaches. In order to obtain such human fragments recognizing glucose oxidase, we used the large synthetic ETH-2 library based on the principle of protein design. Phage displaying glucose oxidase reactive scFvs were obtained after three rounds of selection on glucose oxidase-coated immunotubes and subsequent amplification in TG1 E. coli cells. Eventually, one high reactive scFv clone was selected and further examined. The anti-glucose oxidase scFv C10 was found suitable for Western blot; Biacore analysis showed that the binding affinity of the glucose oxidase-reactive scFv is almost equal that of MAbs prepared with conventional hybridoma technology. Finally, the cDNA sequence of this human scFv may be exploited to generate bispecific antibodies to target in the tumor environment-specific toxic enzymatic reaction.

Abstract. In this study we elucidated the role of ATPbinding cassette (ABC) multi-drug transporter proteins and cellular factors such as Bcl-2 expression and CD33 downmodulation contributing to free and hP67.6 mAb linked calicheamicin-Á1 (CalC-Á1) resistance. We analyzed in a well designed HL60 cell system the relationship between the expression of ABC proteins, Bcl-2 and CD33 modulation with the activity of free and mAb-linked CalC-Á1. The results herein reported and discussed, strongly suggest that both MDR1-Pgp and MRP1 efflux systems are engaged by CalC-Á1, but only MDR1-Pgp over-expression efficiently abrogates drug cytotoxicity in MDR cells. Paradoxically, Bcl-2 expression, as observed for other anticancer compounds belonging to the enediyne family of drugs, confers CalC-Á1 susceptibility rather than resistance in HL60 cells. Further, the isolation of a resistant HL60 subline (HL60AL) that was developed by exposing the parental sensitive cells to subeffective doses of gemtuzumab ozogamicin (GO) over an extended period of time shows a reduced level of CD33 expression that represents an important escape mechanism of HL60 MDR cells to the cytotoxic effect of GO. IntroductionGemtuzumab ozogamicin (GO) is the first clinically validated cytotoxic immunoconjugate in which a humanised anti-CD33 antibody (hP67.6) is covalently linked to a derivative of Calicheamicin-Á1 (CalC-Á1) (1). More recently, the therapeutic potential of CD22-specific antibody-targeted chemotherapy using inotuzumab ozogamicin (CMC-544) is being evaluated at present in Phase I clinical trials in patients with non-Hodgkin's lymphoma (2). Further, a number of tumor-targeted immunoconjugates of CalC-Á1 is being explored preclinically for their therapeutic potential (3,4). However, several factors may affect the efficacy of CalC-Á1 immunoconjugates. These include the common issues of mAb therapy such as antibody specificity, heterogeneous target antigen expression and large inter-individual differences in cellular sensitivity to CalC-Á1 (5). Further, among individuals with de novo AML, the overexpression of the MDR1-P-glycoprotein (MDR1-Pgp), a 170-kDa protein that belongs to the ABC superfamily of proteins, is identified in the 20-75% of malignant cells (6). MDR1-Pgp acts as an efflux pump to remove anticancer drugs from cells, resulting in a simultaneous cross-resistance or multi-drug resistance (MDR) to various chemotherapeutics (7). Although MDR1-Pgp appears to be of biologic and clinical relevance (8), other ABC proteins may be involved in the outcome of GO-treated AML patients (9,10). One such protein, the multi-drug resistance-associated protein (MRP1), is distantly related to MDR1-Pgp, and like MDR1-Pgp, lowers intracellular drug accumulation by promoting drug efflux and MDR (11).Previous studies hypothesized an association between MDR1-Pgp and MRP1 expression and clinical responses to GO (8,12,13), others reported discrepant results attributed to the multi-factorial nature of drug resistance (14,15). Engagement of CD33 by GO results in im...