LEADING EDGE PRODUCT LINES
Human embryonic stem cell (hESC) research has been surrounded by considerable controversy in recent years, particularly with regard to the ethical issues associated with such research. The scientific facts are relatively straightforward.
Regulatory Medicine is a component of Regulatory Affairs that serves as an interface between regulatory agencies and medical scientists in the planning, development, production, and provision of cell and gene therapies and medical devices for the treatment of patients in a clinical setting.
- Document Control- Creation of SOPs, policies, forms, product labels, and worksheets in an appropriate format with versioning and archival histories which meet regulatory standards.
- Validations and Verifications- Creation of thorough plans and schedules for the validation and/or verification of equipment, reagents, and processes used in the development, production, and provision of medical therapies and devices.
- Change Control and Qualification- Management of changes needed to processes and materials that can occur during development and production of medical products, as well as making certain that critical materials and supplies are of the appropriate quality for use in patients.
- Audits and Findings- Development of plans for internal and external audits as well as responses to audit findings.
- Product and Test Report Release- Review of reports for release of products and tests as well as creation of documents for the same purpose that meets regulatory standards.
- Training and Competency- Development of plans, documents, and records to ensure successful training and continued competency of staff members, one of the most often overlooked components of a successful product development.
- Issue Resolution- Plans for management of adverse events, investigations into deviations and incidents, and long-term safety follow-up of products and devices.
- Regulatory Authority Interactions- Preparation for and participation in communication with regulatory authorities during meetings and inspections and follow-up.
- Regulatory Authority Strategy and Intelligence- Knowledge of the ever changing regulatory requirements for implementation of successful studies, processes, and products.
Regulatory Authority Submissions- Application of regulatory strategy and intelligence for the preparation of accurate and successful submissions to regulatory agencies.
Clinical Trial Support
College of American Pathologists (CAP), and the United Network for Organ Sharing (UNOS), ClinImmune Labs and its accredited technical staff are committed to providing the highest quality histocompatibility testing services for research studies as well as clinical transplantation and transfusion programs in Colorado, across the U.S. and abroad.
Testing available for:
- Clinical Transplantation- solid organ and hematopoietic stem cell
- Platelet Transfusion support
- Genetic HLA Disease Association
- Post-Transplant DSA risk and monitoring
Clinically Approved Assays:
- HLA-A, B, C, DRB1/3/4/5, DQA1, DQB1, DPA1, DPB1 loci
- Low to high resolution testing
- HLA Antibody Detection
- Panel Reactive Antibody, including HLA Specificity Analysis
- Titration/Quantitation studies for pre-transplant immunotherapy protocols
- Crossmatching for transplant compatibility
- Platelet support panels to assess allo-reactive HLA antibodies and HLA-A,B typing for selection of matched platelets
- KIR genotyping
- Initial consultations provided for test selection, cost effectiveness, sample and turn-around time requirements
- Immunogenetics testing (e.g. HLA-B*57:01 screening test to determine susceptibility to abacavir hypersensitivity syndrome and HLA-B27 which may assist in the diagnosis of ankylosing spondylitis, juvenile rheumatoid arthritis, and Reiter’s syndrome)
- Transplant Immunology Teleconferences presented at ClinImmune
- Customized requisitions and clear, concise reports; electronic data transfer
- Additional test interpretation consults upon request
- Donor search strategy support
- Analysis of HLA allele frequency
HLA epitope analysis
FDA Licensed Cord Blood
Our research is focused on editing the HLA gene in the peptide binding groove in order to change its ability to bind specific peptides associated with disease. In preliminary studies, we designed a specific mutation in DRB1 to alter the K71 residue found in DRB1*04:01 (an RA-susceptibility allele) to E71, which is found in RA-resistant alleles (e.g., DRB1*01:03 and *04:02); this mutation eliminated collagen binding and the preferential binding of citrullinated peptides. Thus, a single amino acid substitution renders the arthritogenic peptide-binding profile of DRB1*04:01 nearly identical to that of the resistant allele, DRB1*04:02. Although a DRB1-mismatched hematopoietic stem cell transplant to replace DRB1*04:01 could be used to treat RA, the risk of graft-versus-host disease is too high for this to be a viable strategy. However, an autologous hematopoietic stem cell transplant could treat RA by preventing antigen-presenting cells from binding and presenting arthritogenic peptides to T cells.
We are assessing the potential of the CRISPR-Cas9 system to specifically edit genomic DRB1*04:01 to DRB1*04:01K71E in human hematopoietic stem cells while preserving their “stemness.” We propose that performing “plastic surgery” on the patient’s HLA molecule by editing a single amino acid in the HLA gene will introduce the necessary change in DRB1 to halt the progression of RA, while also being safe and avoiding rejection. These studies will provide an essential preclinical evaluation of this novel mode of immunotherapy for the treatment of RA, as a prelude to performing HLA gene editing in humans. Our research will be the first attempt to treat an autoimmune disease by editing individual amino acids within the patient’s own stem cells. If successful, this approach would create entirely new clinical avenues for the treatment of a variety of autoimmune diseases such as multiple sclerosis, Type I diabetes and ankylosing spondylitis.
The ClinImmune Cellular Therapy Laboratory owns the University of Colorado Cord Blood Bank and merged in 2018 with the St. Louis Cord Blood Bank. Both banks are licensed by the United States Food and Drug Administration (FDA).
The laboratory provides hematopoietic stem cell processing for the University of Colorado Hospital Bone Marrow Transplantation Program and is accredited by the Foundation for Accreditation of Cellular Therapy (FACT) and by the College of American Pathologists (CAP).
By combining the infrastructure for stem cell and cord blood processing, ClinImmune Labs achieves significant economies of scale that ensure cost-effective services for our clients.
The ClinImmune Cellular Therapy Laboratory supports a number of clinical cell therapy trials developed by outside companies.