Oral Presentation ISCT ANZ - BAA Joint Scientific Meeting 2022

A pathogen specific T-cell bank generated by activation-induced CD137 selection (80505)

Selmir Avdic 1 2 , Leighton Clancy 3 , Renee Simms 1 2 , Emily Blyth 1 2 4 , David Gottlieb 1 2 4
  1. The University of Sydney, Camperdown, NSW, Australia
  2. Westmead Institute for Medical Research, Westmead, NSW, Australia
  3. Research and Education Network, Western Sydney Local Health District, Westmead, NSW, Australia
  4. Westmead Hospital, Westmead, NSW, Australia

Background:

Immune reconstitution via adoptive transfer of pathogen specific T-cells (PSTs) can control viral infection in immune suppressed patients. We have developed a GMP compliant method for manufacture of enriched PST cell products for important opportunistic infections.

Method: 

HPC-A samples from healthy donors were stimulated with peptide pools of proteins from cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus (AdV) and aspergillus fumigatus (AF) resulting in activation-induced surface expression of CD137. Positive selection of CD137+ cells was performed 16-24 hours post antigen stimulation. These were combined with irradiated CD137neg cells as feeder cells in a G-Rex®-6 device in media supplemented with cytokines IL-2, -7 and -15. Cultures were incubated for a total of 11 days.

Results: 

47 T-cell products were generated specific for CMV (12), EBV (20), AdV (5) and multi-pathogen (CMV, EBV and AF; n=10). Product characteristics are summarised in Table 1.

Antigen specific responses (measured by CD107a/b mobilisation and IFN-γ/TNF-α secretion) are shown in Table 2. HLA restricted responses were present in 11/12 CMV-, 20/20 EBV- and 5/5 AdV-specific products. CMV responses were confirmed using tetramers for HLA-A*02:01 (mean 65.6%), A*24:02 (7.7%), B*07:02 (21.3%) and B*35:01 (5.4%).

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Conclusion: 

We generated a cell bank of CMV, EBV, AdV and multi-pathogen-specific T-cells, using a rapid manufacturing protocol that resulted in highly enriched T-cell products. Products from the cell bank are being utilised in several clinical trials of adoptive immunotherapy.