A novel CXCR4 antagonist IgG1 antibody (PF-06747143) for the treatment of hematologic malignancies.

The chemokine receptor CXCR4 is highly expressed and associated with poor prognosis in multiple malignancies. Upon engagement by its ligand, CXCL12, CXCR4 triggers intracellular signaling pathways that control trafficking of cells to tissues where the ligand is expressed, such as the bone marrow (BM). In hematologic cancers, CXCR4-driven homing of malignant cells to the BM protective niche is a key mechanism driving disease and therapy resistance.

Targeting CD30 in malignant tissues: challenges in detection and clinical applications.

The CD30 transmembrane receptor from the tumor necrosis factor receptor family is expressed in a distinct, yet diverse set of lymphoproliferative disorders and a small subset of normal activated lymphocytes. Therefore, detection of CD30 expression when performed properly according to the standardized methods facilitates diagnosis of Hodgkin lymphoma, anaplastic large cell lymphoma, and other disorders expressing the receptor. More recently, CD30 has also become an attractive therapeutic target.

Characterization of the murine Th2 response to immunization with liposomal M2e influenza vaccine.

While the current influenza vaccine strategy is dependent on eliciting neutralizing antibodies to the hemagglutinin (H or HA) surface glycoprotein, antigenic drifts and occasional antigenic shifts necessitate constant surveillance and annual updates to the vaccine components. The ectodomain of the matrix 2 (M2e) channel protein has been proposed as a universal vaccine candidate, although it has not yet been shown to elicit neutralizing antibodies. Utilizing a liposome-based vaccine technology, an M2e vaccine (L-M2e-HD/MPL) was tested and shown to stimulate the production of anti-M2e antibodies which precipitated with whole virus and inhibited viral cell lysis by multiple type A strains of influenza virus using a novel in vitro assay.

Use of Vaxfectin adjuvant with DNA vaccine encoding the measles virus hemagglutinin and fusion proteins protects juvenile and infant rhesus macaques against measles virus.

A measles virus vaccine for infants under 6 months of age would help control measles. DNA vaccines hold promise, but none has provided full protection from challenge. Codon-optimized plasmid DNAs encoding the measles virus hemagglutinin and fusion glycoproteins were formulated with the cationic lipid-based adjuvant Vaxfectin.

Vaccination with polymerase chain reaction-generated linear expression cassettes protects mice against lethal influenza A challenge.

The feasibility of a linear expression cassette (LEC)-based influenza A DNA vaccine was demonstrated in mice, using a lethal dose (LD90) of a mouse-adapted A/Hong Kong/8/68 (H3N2) influenza strain. LECs expressing hemagglutinin (HA) from either the homotypic H3N2 or the heterotypic H1N1 (A/Puerto Rico/8/34) influenza virus were produced by polymerase chain reaction and either phosphodiester- or phosphorothioate-modified oligonucleotide primers. Survival subsequent to lethal viral challenge was used as a primary end point; weight loss was the secondary end point.

Vaxfectin-formulated influenza DNA vaccines encoding NP and M2 viral proteins protect mice against lethal viral challenge.

Next generation influenza vaccines containing conserved antigens may enhance immunity against seasonal or pandemic influenza virus strains. Using a plasmid DNA (pDNA)-based vaccine approach, we systematically tested combinations of NP, M1, and M2 antigens derived from consensus sequences for protection against lethal influenza challenge and compared formulations for adjuvanting low pDNA vaccine doses. The highest level of protection at the lowest pDNA doses was provided by Vaxfectin-formulated NP + M2.

Cross-reactive neuraminidase antibodies afford partial protection against H5N1 in mice and are present in unexposed humans.

Background: A pandemic H5N1 influenza outbreak would be facilitated by an absence of immunity to the avian-derived virus in the human population. Although this condition is likely in regard to hemagglutinin-mediated immunity, the neuraminidase (NA) of H5N1 viruses (avN1) and of endemic human H1N1 viruses (huN1) are classified in the same serotype. We hypothesized that an immune response to huN1 could mediate cross-protection against H5N1 influenza virus infection.