Engineered red blood cells as an off-the-shelf allogeneic anti-tumor therapeutic.

4-1BB Ligand / genetics Animals Antigen-Presenting Cells / immunology Cell Engineering / methods Cell Line, Tumor Coculture Techniques Disease Models, Animal Erythrocytes / immunology Female HLA-A2 Antigen / genetics Histocompatibility Antigens Class I / genetics Humans Immunotherapy, Adoptive / methods Interleukin-12 / genetics Lymphocyte Activation Neoplasms / immunology Papillomavirus E7 Proteins / genetics Primary Cell Culture T-Lymphocytes / immunology Transplantation, Homologous / methods

Journal

Nature communications

ISSN: 2041-1723

Titre abrégé: Nat Commun

Pays: England

ID NLM: 101528555

Informations de publication

Date de publication:
11 05 2021

Historique:

received: 23 02 2021

accepted: 31 03 2021

entrez: 12 5 2021

pubmed: 13 5 2021

medline: 27 5 2021

Statut: epublish

Résumé

Checkpoint inhibitors and T-cell therapies have highlighted the critical role of T cells in anti-cancer immunity. However, limitations associated with these treatments drive the need for alternative approaches. Here, we engineer red blood cells into artificial antigen-presenting cells (aAPCs) presenting a peptide bound to the major histocompatibility complex I, the costimulatory ligand 4-1BBL, and interleukin (IL)-12. This leads to robust, antigen-specific T-cell expansion, memory formation, additional immune activation, tumor control, and antigen spreading in tumor models in vivo. The presence of 4-1BBL and IL-12 induces minimal toxicities due to restriction to the vasculature and spleen. The allogeneic aAPC, RTX-321, comprised of human leukocyte antigen-A*02:01 presenting the human papilloma virus (HPV) peptide HPV16 E7

Identifiants

DOI: 10.1038/s41467-021-22898-3 PMID: 33976146 PMC: PMC8113241

pubmed: 33976146

doi: 10.1038/s41467-021-22898-3

pii: 10.1038/s41467-021-22898-3

pmc: PMC8113241

doi:

Substances chimiques

4-1BB Ligand 0

HLA-A*02:01 antigen 0

HLA-A2 Antigen 0

Histocompatibility Antigens Class I 0

Papillomavirus E7 Proteins 0

TNFSF9 protein, human 0

oncogene protein E7, Human papillomavirus type 16 0

Interleukin-12 187348-17-0

Types de publication

Journal Article Research Support, N.I.H., Extramural Video-Audio Media

Langues

eng

Sous-ensembles de citation

Pagination

2637

Subventions

Organisme : NINDS NIH HHS

ID : P30 NS072030

Pays : United States

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