Viventia Bio (Canada)

Characterize patient reported pain in neuromyelitis optica spectrum disorder (NMOSD) in the N-MOmentum study of inebilizumab.

A distinct B cell population marked by elevated CD11c expression is found in patients with systemic lupus erythematosus (SLE). Cells with a similar phenotype have been described during chronic infection, but variable gating strategies and nomenclature have led to uncertainty of their relationship to each other. We isolated CD11chi cells from peripheral blood and characterized them using transcriptome and IgH repertoire analyses. Gene expression data revealed the CD11chi IgD+ and IgD− subsets were highly similar to each other, but distinct from naive, memory, and plasma cell subsets. Although CD11chi B cells were enriched in some germinal center (GC) transcripts and expressed numerous negative regulators of B cell receptor (BCR) activation, they were distinct from GC B cells. Gene expression patterns from SLE CD11chi B cells were shared with other human diseases, but not with mouse age-associated B cells. IgH V-gene sequencing analysis showed IgD+ and IgD− CD11chi B cells had somatic hypermutation and were clonally related to each other and to conventional memory and plasma cells. However, the IgH repertoires expressed by the different subsets suggested that defects in negative selection during GC transit could contribute to autoimmunity. The results portray a pervasive B cell population that accumulates during autoimmunity and chronic infection and is refractory to BCR signaling.

To characterize long-term efficacy and safety of inebilizumab in neuromyelitis optica spectrum disorder (NMOSD).

Abstract VB6-845d is a Targeted Protein Therapeutic, TPT, that comprises a Fab fragment specific for the Epithelial Cell Adhesion Molecule (EpCAM) genetically fused to deBouganin via a furin protease sensitive linker. DeBouganin (deB) is a de-immunized variant of bouganin, a ribosome inactivating protein (RIP), that when internalized blocks protein synthesis thereby leading to cell death. While all cytotoxic molecules induce tumor cell killing, only some are capable of inducing biological manifestations indicative of immunogenic cell death (ICD). ICD is characterized by the collective appearance of distinct cellular changes termed damage associated molecular patterns, or DAMPs, which play a role in immune cell activation by triggering pro-inflammatory processes. Key DAMPs necessary for defining ICD are cell surface translocation of calreticulin, an endoplasmic reticulum chaperone protein, ATP secretion and release of HMGB1 (high mobility group box 1). To evaluate whether VB6-845d cell killing elicits the hallmark features of ICD, VB6-845d treated tumor cell lines were assessed for the presence of these distinct signaling molecules. In vitro studies showed that VB6-845d cytotoxicity induces the translocation of calreticulin to the cell surface as well as the release of ATP and HMGB1. The expression of other potential immune regulators following VB6-845d treatment was also examined. In summary, the data presented suggests that VB6-845d mediates tumor cell killing by an ICD pathway. The potential cross-priming effect initiated by VB6-845d-induced ICD suggests the use of VB6-845d in combination with immune checkpoint inhibitors may enhance their effectiveness in EpCAM-positive epithelial cancers. Citation Format: Rachelle L. Dillon, Shilpa Chooniedass, Arjune Premsukh, Glen C. MacDonald, Jeannick Cizeau, Gregory P. Adams. VB6-845d tumor cell killing elicits biologic features of immunogenic cell death [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2788.

Antibody Engineering & Therapeutics, the annual meeting of The Antibody Society, will be held in San Diego, CA in early December 2015. In this meeting preview, the chairs provide their thoughts on the importance of their session topics, which include antibody effector functions, reproducibility of research and diagnostic antibodies, new developments in antibody-drug conjugates (ADCs), preclinical and clinical ADC data, new technologies and applications for bispecific antibodies, antibody therapeutics for non-cancer and orphan indications, antibodies to harness the cellular immune system, overcoming resistance to clinical immunotherapy, and building comprehensive IGVH-gene repertoires through discovering, confirming and cataloging new germline IGVH genes. The Antibody Society's special session will focus on “Antibodies to watch” in 2016, which are a subset of the nearly 50 antibodies currently in Phase 3 clinical studies. Featuring over 100 speakers in total, the meeting will commence with keynote presentations by Erica Ollmann Saphire (The Scripps Research Institute), Wayne A. Marasco (Dana-Farber Cancer Institute/Harvard Medical School), Joe W. Gray (Oregon Health & Science University), and Anna M. Wu (University of California Los Angeles), and it will conclude with workshops on the promise and challenges of using next-generation sequencing for antibody discovery and engineering from synthetic and in vivo libraries and on computational antibody design.

An understanding of the population dynamics and habitat of wild Red Foxes (Vulpes vulpes) and Coyotes (Canis latrans) is a prerequisite to wildlife management. This information is also important in assessing the risk these wild canids pose to the public and domestic animals. On Prince Edward Island, information on age, sex, reproductive activity, and habitat use of 271 Red Foxes and 201 Coyotes was collected in the hunting and trapping season of 2004–2005. The estimated age of Red Foxes and Coyotes ranged from 0.5 to 13.5 years. A large proportion of harvested Red Foxes and Coyotes (58% and 48%, respectively) consisted of juveniles. The sex ratio was not significantly different from 1:1 for either species. Average litter size was 5.0 and 5.2 for Red Foxes and Coyotes, respectively. Number of placental scars ranged from 0 to 7 in Red Foxes and from 0 to 11 in Coyotes. Agricultural areas were the main habitat type (52%) of harvested Red Foxes. For harvested Coyotes, forest was the main habitat (44%), followed closely by agricultural areas (43%). Urban areas were a significant part (13%) of the habitat of Red Foxes. These data can be used to monitor population dynamics over time, provide information for wildlife management, and provide information on potential risk areas for disease transmission by wild canids.

4580 Background: Vicinium is a fusion protein comprised of a humanized scFv, specific for Ep-CAM (epithelial cell adhesion molecule), and a truncated fragment of Pseudomonas exotoxin A. Ep-CAM is highly expressed on carcinoma cells including superficial transitional cell carcinomas (TCC) of the bladder. Vicinium targets and kills Ep-CAM-positive tumors. Results from the Phase I arm of a Phase I/II trial where Vicinium was instilled into the bladders of patients with superficial TCC of the bladder showed the drug to be very well tolerated and showed promising clinical results. Methods: 64 patients with Ep-CAM positive superficial TCC of the bladder, Ta, Tis or T1, Grades 2 or 3 who were refractory or intolerant to BCG therapy were admitted into the study. Dosing comprised a minimum of 3 subjects per dose level through 12 escalating doses. Vicinium was given once/week for 6 consecutive weeks by intravesical administration into the bladder via a catheter at escalating dose levels of 0.1, 0.2, 0.33, 0.66, 1.32, 2.64, 5.28, 10.56, 13.73, 17.85, 23.2 and 30.16 mg/week. All toxicities were assessed according to the NCI CTC v3. Blood samples were collected at different times in the study to determine systemic drug exposure and to assess immunogenicity. Efficacy was explored via biopsy, cystoscopy, urine cytology and FISH. Results: Vicinium was very well tolerated at all doses. Almost all (64/65) patients were positive for the Ep-CAM antigen. Pharmacokinetic analysis showed no evidence of Vicinium in the circulation of any of the patients; however, the majority of patients developed an anti-Vicinium response. Most patients, in particular at the higher doses, showed decreased tumor cell numbers by FISH analysis by the final day of treatment with the greatest sustained effect being observed in patients with the higher percentage Ep-CAM-positive tumors. Conclusions: Vicinium dosed on a weekly basis for 6 weeks was very well tolerated at all dose levels. The early clinical benefit observed with Vicinium strongly supports its development as a promising therapy for superficial transitional cell carcinoma of the bladder. The phase II arm of the trial will confirm the safety and further assess the efficacy of Vicinium at a recommended Phase II dose. [Table: see text]