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NMOSD Donor PBMCs: AQP4-IgG Biology, Complement Activation, and Neuromyelitis Optica Research

Research Use Only (RUO). All OrganaBio disease-state donor material is intended for laboratory research, drug discovery, and non-clinical studies only. Not for therapeutic, diagnostic, or clinical manufacturing use.

Reviewed by Sarah Alter, Ph.D. — Scientific Affairs, OrganaBio. 15 years of immunology research spanning autoimmunity, cancer, and infectious disease. University of Miami Miller School of Medicine. Registered Patent Agent.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy characterized by severe, relapsing attacks of optic neuritis and transverse myelitis. In 70-80% of patients, IgG1 antibodies against aquaporin-4 (AQP4-IgG) — a water channel expressed on astrocyte end-feet at the blood-brain barrier — are the defining pathogenic autoantibody. AQP4-IgG activates complement at the CNS entry point, triggers ADCC by NK cells and eosinophils, and drives astrocyte destruction that produces secondary demyelination and inflammatory infiltration. The NMOSD therapeutic pipeline is exceptionally rich relative to disease prevalence: eculizumab (anti-C5), inebilizumab (anti-CD19), satralizumab (anti-IL-6R), ublituximab (anti-CD20), and rozanolixizumab (FcRn inhibitor) represent five distinct approved or late-stage mechanisms, each addressable through PBMC-based pharmacodynamic research.

AQP4-IgG Versus MOGAD: Mechanistic Distinctions for Research Design

Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) affects approximately 20-30% of patients previously classified as AQP4-IgG-negative NMOSD. MOGAD has a distinct mechanism from AQP4-IgG NMOSD:

  • Anti-MOG antibodies target a myelin surface protein (MOG) rather than an astrocyte water channel; the primary target is oligodendrocyte myelin, producing a pattern closer to MS than astrocytopathy
  • Complement activation is less prominent in MOGAD than AQP4-IgG NMOSD — MOG-IgG1 activates complement but the IgG titer-response relationship for complement activation differs
  • T cell contribution is relatively more prominent in MOGAD; Th17 cells are elevated and the T cell-mediated mechanism may be more relevant to demyelination in MOGAD than in AQP4-IgG NMOSD
  • Clinical outcomes are generally better in MOGAD (less disability accumulation, better relapse recovery)

For complement C5 inhibitor development, NK cell ADCC studies, and inebilizumab pharmacodynamics, AQP4-IgG NMOSD donors are the appropriate disease context. For Th17 biology and T cell-mediated neuro-inflammatory studies, MOGAD cohorts may be more mechanistically relevant.

The Three Approved NMOSD Mechanisms: PBMC Pharmacodynamic Platforms

Eculizumab (anti-C5) — complement pathway: AQP4-IgG IgG1 activates C1q → classical pathway → C5 cleavage → C5a (anaphylatoxin, monocyte activator) + C5b → MAC formation on astrocytes. Monocyte C5aR1 expression and C5a-driven cytokine production in NMOSD PBMCs provide the systemic complement activation readout for C5 inhibitor pharmacodynamics — analogous to the ANCA vasculitis C5aR1 platform but driven by AQP4-IgG-mediated rather than ANCA-mediated complement activation.

Inebilizumab (anti-CD19) — B cell depletion: CD19 is expressed on all B cells including CD20-low plasmablasts and plasma cell precursors that have downregulated CD20. Anti-AQP4-producing plasmablasts in NMOSD peripheral blood express low or negligible CD20 while retaining CD19, making inebilizumab a broader depletion agent than rituximab for eliminating the AQP4-IgG-producing cell pool. NMOSD PBMCs enable direct measurement of CD20 versus CD19 expression on AQP4-secreting plasmablasts, validating the mechanistic rationale for CD19 over CD20 targeting in this indication.

Satralizumab (anti-IL-6R) — IL-6 pathway: IL-6 is elevated in NMOSD CSF and blood during attacks; IL-6 signaling drives Th17 cell differentiation, plasma cell survival, and blood-brain barrier permeability. PBMC pharmacodynamic assays for satralizumab include STAT3 phosphorylation inhibition (IL-6 downstream) in NMOSD T cells and monocytes, Th17 differentiation suppression under IL-6 conditions, and AQP4-specific IgG production reduction in IL-6-supported NMOSD plasmablast cultures.

NK Cell Biology and ADCC in NMOSD

Following AQP4-IgG IgG1 binding to astrocyte AQP4, NK cells and eosinophils recognize IgG-opsonized target cells via FcgammaRIII (CD16) and execute ADCC. NK cells from NMOSD peripheral blood show elevated activation markers and CD16 expression, particularly during acute attacks. NMOSD donor NK cells can be used as effectors in ADCC assays against AQP4-expressing astrocyte-like target cells (e.g., AQP4-transfected cell lines), providing a functional NK-ADCC readout for:

  • Comparing ADCC potency of NMOSD versus healthy donor NK cells against AQP4-expressing targets
  • Measuring FcgammaR-blocking or NK cell-depleting strategy pharmacodynamics
  • Studying the relative contribution of complement MAC versus ADCC to astrocyte destruction in AQP4-IgG NMOSD

IL-6 Pathway Biology in Peripheral Blood

IL-6 signaling in NMOSD drives multiple pathological processes accessible in peripheral blood:

  • Th17 cell expansion — elevated circulating Th17 cells in active NMOSD correlate with attack frequency and CSF IL-6 levels
  • Plasmablast maintenance — IL-6 supports the survival and antibody secretory function of anti-AQP4-producing plasmablasts; IL-6R blockade reduces plasmablast frequency and AQP4-IgG titer
  • STAT3 activation in monocytes — measurable as a direct pharmacodynamic readout for satralizumab and tocilizumab in NMOSD PBMC assay systems

Research Applications

  • Complement C5 inhibitor pharmacodynamics: Monocyte C5aR1 expression, C5a-driven cytokine activation, MAC generation in AQP4-IgG-activated complement conditions
  • CD19 versus CD20 B cell depletion comparison: Plasmablast CD19/CD20 expression profiling, AQP4-specific B cell ELISPOT, depletion coverage analysis for inebilizumab vs. rituximab
  • IL-6R pharmacodynamics (satralizumab, tocilizumab): STAT3 phosphorylation inhibition, Th17 suppression, plasmablast survival reduction in IL-6-supported cultures
  • FcRn inhibitor development: Monocyte FcRn expression in NMOSD context, AQP4-IgG (IgG1) recycling inhibition assays, IgG1-specific catabolism pharmacodynamics
  • NK cell ADCC characterization: NMOSD NK cell activation profiling, FcgammaRIII expression, ADCC potency against AQP4-expressing targets
  • AQP4-specific B cell biology: Anti-AQP4 plasmablast enumeration, AQP4-reactive memory B cell isolation, attack-phase vs. remission B cell compartment comparison

OrganaBio NMOSD Donor Collection Specifications

  • Diagnosis by 2015 International Panel criteria; AQP4-IgG status documented (seropositive vs. seronegative/MOG-IgG-positive)
  • AQP4-IgG titer at collection; MOGAD cohort (anti-MOG IgG) available separately
  • Disease phase: acute attack versus remission; time from most recent attack documented
  • Prior treatment history: eculizumab, inebilizumab, satralizumab, rituximab, IVIG, plasma exchange documented
  • Same-day processing from apheresis; 30-minute standard; >80% post-thaw viability
  • Available as isolated PBMCs, leukopaks (for NK cell ADCC studies), or fresh whole blood

Related resources: CIDP Donor PBMCs: FcRn biology and paranodal IgG4 | ANCA Vasculitis Donor PBMCs: complement C5aR1 pharmacodynamics

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Andrew Larson

Managing Director, CPC Services

Andrew joins OrganaBio as a project manager with varied experience in project management, client relations, and process improvement.

Prior to OrganaBio, Andrew was a client relations manager for the cGMP nucleic acids business unit at Aldevron, coordinating and managing contracts at each stage of the contract lifecycle in support of cell and gene therapy program development. Andrew supported small- and large-scale biotechnology and pharmaceutical clients anywhere from pre-IND work through commercial supply chain establishment. Before Aldevron, Andrew was a project manager for the commercialization and business development department for Sanford Health, a worldwide hospital institution. At Sanford Health, Andrew helped manage medical device patent and prototype development efforts for employee innovations primarily in the cardiovascular, neurovascular, and software spaces. Andrew was also an engineer for Atirix Medical Systems and supported the buildout of automated analysis worksheets to streamline radiology department quality control procedures.

Andrew received his Bachelor of Science in Physics from Minnesota State University Moorhead and his Master of Science in Biomedical Engineering from the University of Minnesota. At the University of Minnesota, Andrew was part of the Center for Magnetic Resonance Research, assisting efforts to automate MRI dataset registration and workflow improvement.

Michael Dee

Associate Director, QC and Analytical Development

Michael Dee has spent the last 17 years researching the immune system. Initially studying the recombinant cytokine IL-2 and its role in T cell subset differentiation and function at the University of Miami. He also helped elucidate the lower level of TCR diversity of T regs required to prevent autoimmunity in mice. Michael also supported construction, cloning, production, purification, and testing both in vitro and in vivo a novel IL-2/IL2Rα complex currently under clinical development with BMS. Michael also was a member of the department of immunology’s program project delineating the effect of a novel Eg7GP96 heat shock protein vaccine on tumor immunity.

While at Immunity Bio (formerly Altor Biosciences), he helped to characterize over 20 novel drugs for immune modulation and treatment of cancer.  After Immunity Bio, Michael was a founding team member of HCW Biologics, where he continued his role in design and initial production and characterization of several novel biologics. He has experience with proof of principle experiments with the generation CAR-NK and CAR T cells. His research at HCW was highlighted by his discovery of a process using novel biologics to activate and expand CIML NK cells. The process and rights were sold to Wugen and is currently in Phase I clinical trials. He also is listed as an Inventor on patent number: US20210268022A1 on method of activating regulatory T cells.

Meram Alamoudi

Senior Cell Processing Specialist

Meram received her master’s degree in biomedical sciences from Barry University and bachelor’s in Biology from Palm Beach Atlantic University.

Before her position at OrganaBio, Meram conducted research at Larkin University where she worked on assessing the impact of Hurricane Maria on respiratory diseases in Puerto Rico, which provided her with insight into research investigation and analysis along with generation of grant documentation.

Valeria Beckhoff-Ferrero

Senior Bioprocess Scientist

Valeria Beckhoff Ferrero has over 8 years of experience in the fields of stem cell research and tissue engineering. Valeria received her Bachelor of Science in Biomedical Engineering, specializing in Biomaterials and Tissue Engineering, from Drexel University in Philadelphia. Valeria has expertise in problem solving and finding manufacturing solutions for isolating various types stem cells and other cell derived products from different tissues.

Before joining OrganaBio, Valeria was a lead manufacturing engineer at the Amnion Foundation. She aided in instituting a GMP infrastructure, including documentation, to manufacture clinical grade placental derived stem cells. In her role, she worked in perfecting isolation, culture, selection and cell maintenance processes for perinatal derived stem cells.

Valeria’s experience includes working as an Automation Engineer at the New York Stem Cell Foundation, where she aided in the creation and coding procedures for liquid handlers to manufacture induced pluripotent stem cells. At NYSF, Valeria researched new methods of sorting, reprogramming and differentiating iPSCs.

During her studies, Valeria worked at Thomas Jefferson University Hospital’s Radiation Oncology department, where she engineered various devices to aid in hyperthermia treatments. Additionally, Valeria co-authored multiple publications on magnetic resonance guided focused ultrasound and radiation antennas for hyperthermia treatments.

Marisa Reinoso

Director, Regional Scientific Sales

Marisa has experience leading marketing and sales life sciences programs for over a decade. Originally a lab researcher, she made the jump to marketing & sales in life sciences and never looked back.

At OrganaBio, she connects cell therapy developers on the West coast and in Asia with the healthy donor starting materials they need to develop their therapies. Prior to OrganaBio, she was the cell therapy marketing lead at Invetech, heading the launch of the company’s first cell therapy product. Marisa has led marketing programs at clinical supply companies Sherpa Clinical Packaging and PCI Pharma Services. In her spare time, Marisa enjoys traveling, eating, and pretending she’s a tennis player. She has a Bachelor of Arts in Biology from Reed College and an MBA from Portland State University.

Thelma Cela

Senior Director, Tissue Procurement

Thelma Cela is a top performing professional with over 25 years’ experience in management, leadership, business development and marketing fields with business acumen and skills in driving revenue and profit growth in multiple corporate cultures. Prior to joining OrganaBio, Thelma served as Senior Director for Health and Human Services for the Seminole Tribe of Florida. Her role had oversight for health clinics, health plan administration, the behavioral health department, and elder services. In this governmental administrative capacity, Thelma had primarily responsibility for the HHS’ divisions’ budget, capital projects, utilization management, efficiency, and efficacy.

Thelma’s prior work experiences include Vice President of Clinical Operations for OrthoNOW. In this role, she provided guidance on all clinical matters, set direction on clinical policies and procedures and monitoring healthcare policy changes. As the national Vice President of Clinical Operations, Thelma also designed, developed, and implemented guidelines and protocols and ensured compliance regarding overall patient experience.

Before joining OrthoNOW, Thelma had been recruited by Leon Medical Centers, a private healthcare company operating comprehensive medical centers to launch a new business line addressing the health and wellness of an aging population. As Director, Thelma researched, created, and launched the company’s Health Living Centers which provided first of its kind facilities in the South Florida market to offer services to the community of health aging.

Thelma has a proven track record in multiple corporate healthcare cultures having worked for Mercy Hospital where she was Senior Program Director of their Diabetes Treatment Center and Director of their Surgical Weight Loss Program. She enhanced these service lines awareness in the community, improved both lines’ clinical outcomes, and built volume growth while maintaining ongoing physician support. She served in a similar capacity for American Healthways.

Thelma earned her MBA from Miami Regional University where she graduated Cum Laude and her undergraduate degree in Psychology is from the University of Miami.

She serves on the advisory panel for Florida International University’s Women in Business Leadership Program helping future women become future business leaders through thought leadership, barrier destruction, and the power of influence.

Dominic Mancini

Vice President, Operations

Dominic Mancini brings 12 years of experience working the interfaces between Analytical Development, Process Development, Quality, and Manufacturing Science to OrganaBio. A lifelong learner, Dominic enjoys solving the many scientific and operational challenges presented in the field of cell and gene therapy.

Prior to OrganaBio, Dominic spent 8 years at Bluebird Bio as the company grew from 45 to 1200+ employees and from 1 clinical asset to a robust commercial pipeline. At Bluebird, Dominic initially supported the development and technology transfer of lentiviral vector manufacturing processes. As demand grew for lentiviral process and product characterization, Dominic led the development, qualification, transfer, and validation two commercial release methods. Dominic transitioned back to the Process Development organization to lead the vector manufacturing core team, increasing operational efficiency through a 5S implementation, process schedule intensification, and reverse technology transfer initiative. More recently, Dominic supported the build-out of bluebird’s Manufacturing Science & Technology team followed by the Data Systems & Analytics team, handling late-stage commercial asset support.

Dominic received his Bachelor of Chemical Engineering with Distinction from the University of Delaware. Dominic’s undergraduate research culminated in his thesis on heterologous expression of G-protein coupled receptors in Saccharomyces cerevisiae. After graduation, Dominic was the premier hire of the Zhou Laboratory at Brigham and Women’s hospital in Boston, MA. In three years, Dominic established an animal model of COPD and co-authored several papers with his collaborators in the Pulmonary division.

Christopher B. Goodman

Vice President, Quality & Regulatory Affairs

Christopher B. Goodman is a biopharmaceutical consultant and executive making a global impact in the cellular therapy technology arena. The scope of Christopher’s expertise encompasses Cellular Therapeutic Operations, Quality and Regulatory Affairs, Global Corporate Operations, Scientific Strategic Planning, Scientific R&D Collaborations, and Marketing & Commercialization.

Christopher recently joined OrganaBio as their Vice President of Regulatory Affairs. In this role, Christopher will be helping the company, its clients and partners navigate the complexities of the domestic and international regulatory requirements governing advanced cellular therapy products and manufacturing.

Previously, Christopher held positions with the Association for the Advancement of Blood and Biotherapies (AABB), Virgin Health Bank, Ventana Medical Systems, and Celgene.

While with AABB, he held the positions of Senior Director of New Products and Lead Quality Assessor, auditing both domestic and international organizations to known standards in an effort to promote and ensure patient quality care and manufactured product consistency and standardization within Cellular Therapy, Blood Banking, Transfusion Services, Perioperative and Donor Center industries and operations. He contributed greatly to the work of AABB’s accreditation program providing his deep breadth of knowledge and technical acumen on many committees during his tenure. His pioneering work in the realm of virtual assessments during the COVID pandemic allowed AABB to flex into the planning and execution of this novel approach to the maintenance of accreditation activities during a global travel crisis. His agile thinking and approach to planning provided as minimal disruption as possible to AABB’s customer facilities.

While working with Virgin Health Bank in the State of Qatar and the United Kingdom, Christopher advanced through a series of executive roles. He joined Virgin Health Bank as the Director of Operations, during which time he managed the successful design, and build out of a new state-of-the-art cGMP facility, the first in the Middle East. As Director and Chief Executive Officer, he directed the launch of the first Arab-centric stem cell bank, and strategically guided the organization to enhanced shareholder value and expansion across the Middle East and UK. In these roles, he also oversaw global corporate operations, research collaborations, product portfolio expansion, and regulatory framework.

Christopher managed the Detection and Chemistry Assay Development Group for Ventana Medical Systems, a global leader and innovator of tissue-based diagnostic solutions. In this role, he directed overall program goals, optimized resources, and guided technical and product direction in global regulated environments.

Prior to Ventana Medical Systems, he held the position of Director of Operations for the high-growth Cellular Therapeutics Division of Celgene. As a senior-level scientist and member of the executive team, he directed divisional operations, medical affairs and executed business and scientific strategic planning.

Danielle Smyla

Senior Director, Quality Assurance

Danielle Smyla, M.S., brings 14 years of Quality Assurance and GMP experience in the Biotechnology and Medical Device industries. Ms. Smyla is an established Quality Leader with expertise in the implementation, management and continuous improvement of Quality Management Systems for GMP operations.

Prior to joining OrganaBio, Danielle was a key member of the Quality Management team at Canon BioMedical, where she led the cross-functional development and implementation of their Quality Management System. She also managed a team of Quality Specialists and Sr. Specialists, coaching them in the implementation, management and identification of improvements to quality processes.

Ms. Smyla’s Quality-focused career is complimented by valuable hands-on experience in GMP product manufacturing, as well as R&D laboratory experimentation and formulation work in support of product development.

Danielle has earned a Master’s in Biotechnology from the Johns Hopkins University and a Bachelor of Science in Chemistry from the George Washington University.

Sarah Alter, Ph.D.

Lab Director

Sarah Alter, Ph.D., is Laboratory Director at OrganaBio, LLC, where she provides technical leadership across laboratory operations, process development, product manufacturing, and clinical sample processing services supporting cell and gene therapy developers worldwide. She brings more than 20 years of immunology and translational research experience spanning autoimmunity, oncology, and infectious disease.

Since joining OrganaBio in 2018, Dr. Alter has progressed through roles of increasing responsibility, first as Director of Immunology, leading development and manufacturing of human-derived immune cell products for immuno-oncology partners and clients; then as Senior Director of Scientific Affairs, where she served as immunology subject matter expert and shaped scientific strategy across new product launches, market analyses, and client engagements. She also served as founding Managing Director of HemaCenter, LLC, OrganaBio’s FDA-registered leukapheresis collection subsidiary, where she stood up operations, recruited the medical team, and authored governing protocols and SOPs.

Earlier in her career, Dr. Alter led preclinical R&D for IL-15–based immunotherapies at Altor BioScience (now ImmunityBio), contributing to programs that advanced into the clinic and co-authoring numerous peer-reviewed publications. She holds a Ph.D. in Immunology from the University of Miami Miller School of Medicine and an M.Sc. in Microbiology from Florida Atlantic University, and is a registered Patent Agent licensed to practice before the U.S. Patent and Trademark Office.

Carlos Carballosa, Ph.D

Vice President, Sales

Dr. Carlos Carballosa holds a doctorate in Biomedical Engineering from the University of Miami and currently leads global sales for OrganaBio as the VP of Sales. Since joining the company in 2018, Carlos has had a hand in managing all of OrganaBio’s products and services including perinatal tissue, apheresis material, and cell processing and cryopreservation support services for clinical trials.

Oscar Robles

Director, Quality Systems

Oscar Robles has over thirty years of experience in pharmaceutical and medical device industries. His main areas of expertise are in Quality Systems, Quality Assurance, Manufacturing Systems Validation, Computerized Systems Validation, implementation of GxP Computerized Systems and ERP Systems such as TrackWise, Electronic Document Management, JDEwards, SAP, and Oracle. Prior to joining OrganaBio, Oscar was a member of the Quality Management team at Apotex – Aveva Drug Delivery Systems for ten years. Oscar has earned a Master’s in Business Administration from Nova Southeastern University and a Bachelor of Science in Electrical Engineering from Florida International University.

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