Unbiased cell surface proteomics identifies SEMA4A as an effective immunotherapy target for myeloma.
Blood
; 139(16): 2471-2482, 2022 04 21.
Article
en En
| MEDLINE
| ID: mdl-35134130
ABSTRACT
The accessibility of cell surface proteins makes them tractable for targeting by cancer immunotherapy, but identifying suitable targets remains challenging. Here we describe plasma membrane profiling of primary human myeloma cells to identify an unprecedented number of cell surface proteins of a primary cancer. We used a novel approach to prioritize immunotherapy targets and identified a cell surface protein not previously implicated in myeloma, semaphorin-4A (SEMA4A). Using knock-down by short-hairpin RNA and CRISPR/nuclease-dead Cas9 (dCas9), we show that expression of SEMA4A is essential for normal myeloma cell growth in vitro, indicating that myeloma cells cannot downregulate the protein to avoid detection. We further show that SEMA4A would not be identified as a myeloma therapeutic target by standard CRISPR/Cas9 knockout screens because of exon skipping. Finally, we potently and selectively targeted SEMA4A with a novel antibody-drug conjugate in vitro and in vivo.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Semaforinas
/
Mieloma Múltiple
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Blood
Año:
2022
Tipo del documento:
Article