Role of the Blood Services in the Provision of ATMPs

Background

• The cells required for therapeutic manufacture are obtained from multiple sources and include various cell types. The living drug nature of cellular therapies, which allows for their expansion and persistence in the patient, highlights the crucial role that the donated starting material(s) plays throughout the manufacturing process.
• Identification of stable and ethically-sourced cells for manufacture is a significant challenge and must be coupled with strong end-to-end (donor-patient) linkage, as well as post-treatment vigilance.
• Personalisation also infers the critical need for detailed evaluation and characterisation, of donors and donated material, respectively.
• Harmonising research endeavours from SoHO to ATMP, or Donor to Recipient, with good manufacturing production (GMP) and licencing regulation is essential.
• The Irish Blood Transfusion Service (IBTS) operates a mature and robust “vein-to-vein” ecosystem.
• Furthermore, despite the efficacy of allogeneic stem cell transplantation in treating blood cancers, a significant number of patients relapse and/or experience post-treatment complications. Correlation of patient biomedical assessments post transplantation with clinical outcomes is criticial to identify potential prognostic biomarkers for treatment response.

Aims

1. What are the most appropriate criteria for evaluating the eligibility of allogeneic donors, and their
donated material?

• This directly addresses the regulatory link between SoHO and ATMP regulation.
• Considers the requirements for donor recruitment, donor qualification, HLA-typing and matching, Infectious disease screening, collection method, consenting process and bio-
  banking.

2. How can ‘unwanted’ donated biological material be re-purposed for cellular therapy research, development and manufacture?

• Laboratory analysis of cell types recovered from leucoreduction filters following blood component production
  Considerations for platelet lysate production, and its use in cellular therapeutic research and GMP manufacture.
  Manufacture and licencing of Virus-Specific T cells as a minimally manipulated cellular therapeutic treatment for transplant patients with virus reactivation.

3. What is the optimum framework for cellular therapy manufacture from donated material in Ireland?

• What regulatory components must be considered for manufacture, licencing and authorisation of different cellular therapies in Ireland?
  Determine the ethical implications of re-purposing voluntary non-remunerate donated (VNRD) material for commercial manufacture (and possibly financial gain). 
• Develop an Irish business model for the commercial manufacture of cellular therapies using ‘unwanted’ donated material?

4. What is the optimum immune monitoring laboratory alogirthm for patients post-cellular therapy  transplantation?

• Prospectively monitor patients and biobank samples at serial time points post allogeneic stem cell transplantation and CAR-T cell therapy.
• Examine immune cell subsets and killer cell immunoglobin-like receptor (KIR) profiles in the allogeneic stem transplant cohort.
• Examine immune cell subsets, CAR-T cell persistence and exhaustion marker phenotypes in the CAR-T cell therapy cohort.
• Identify determinants of successful immune reconstitution and favourable clinical outcomes after allogeneic stem cell transplantation and CAR-T cell therapy.
• Identify determinants of unsuccessful immune reconstitution and poor clinical outcomes post-allo-SCT and CAR-T cell therapy.

Cellular Therapy Research Group (CTRG)

1. St James Hospital
2. Irish Blood Transfusion Service
3. Trinity Translational Medicine Institute
4. Trinity College Dublin

BTCs4ATMP - EU COST Action