PMID- 37294945
OWN - NLM
STAT- MEDLINE
DCOM- 20230802
LR  - 20230802
IS  - 1538-8514 (Electronic)
IS  - 1535-7163 (Linking)
VI  - 22
IP  - 8
DP  - 2023 Aug 1
TI  - ABBV-184: A Novel Survivin-specific TCR/CD3 Bispecific T-cell Engager is Active 
      against Both Solid Tumor and Hematologic Malignancies.
PG  - 903-912
LID - 10.1158/1535-7163.MCT-22-0770 [doi]
AB  - CD3 bispecific T-cell engagers (TCE), comprised of a tumor-targeting domain 
      linked to a CD3 binding domain, function by bridging target-positive tumors and 
      CD3-expressing effector T cells enabling redirected T cell-mediated killing of 
      tumor cells. Although the majority of CD3 bispecific molecules in clinical 
      development incorporate tumor-targeting antibody-based binding domains, many 
      tumor-associated antigens derive from intracellular proteins and are not 
      accessible to targeting via antibody. Intracellular proteins processed into short 
      peptide fragments and presented on the cell surface by MHC proteins are 
      recognized by T-cell receptors (TCR) on the surface of T cells. Here we describe 
      the generation and preclinical evaluation of ABBV-184, a novel TCR/anti-CD3 
      bispecific composed of a highly selective soluble TCR that binds a peptide 
      derived from the oncogene survivin (BIRC5) bound to the class I MHC allele human 
      leukocyte antigen (HLA)-A*02:01 expressed on tumor cells, linked to a specific 
      binder to the CD3 receptor on T cells. ABBV-184 drives an optimal distance 
      between T cell and target cell thereby enabling sensitive recognition of 
      low-density peptide/MHC targets. Consistent with the expression profile of 
      survivin across a broad range of both hematologic and solid tumors, treatment of 
      acute myeloid leukemia (AML) and non-small cell lung cancer (NSCLC) cell lines 
      with ABBV-184 results in T-cell activation, proliferation, and potent redirected 
      cytotoxicity of HLA-A2-positive target cell lines, both in vitro and in vivo, 
      including patient-derived AML samples. These results indicate that ABBV-184 is an 
      attractive clinical candidate for the treatment of patients with AML and NSCLC.
CI  - (c)2023 American Association for Cancer Research.
FAU - Chervin, Adam S
AU  - Chervin AS
AUID- ORCID: 0009-0007-4185-1345
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - Stone, Jennifer D
AU  - Stone JD
AUID- ORCID: 0000-0001-5654-5825
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - Konieczna, Iwona
AU  - Konieczna I
AUID- ORCID: 0009-0005-1998-6310
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - Calabrese, Kelly M
AU  - Calabrese KM
AUID- ORCID: 0000-0002-6184-3269
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - Wang, Ningyan
AU  - Wang N
AUID- ORCID: 0009-0004-3183-4777
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - Haribhai, Dipica
AU  - Haribhai D
AUID- ORCID: 0009-0005-3274-7410
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - Dong, Feng
AU  - Dong F
AUID- ORCID: 0009-0000-3866-7714
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - White, Michael K
AU  - White MK
AUID- ORCID: 0009-0004-5301-8711
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - Rodriguez, Luis E
AU  - Rodriguez LE
AUID- ORCID: 0009-0007-2408-5394
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - Bukofzer, Gail T
AU  - Bukofzer GT
AUID- ORCID: 0009-0005-1597-4953
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - Ellis, Paul A
AU  - Ellis PA
AUID- ORCID: 0009-0005-0179-7124
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - Cosgrove, Cormac
AU  - Cosgrove C
AUID- ORCID: 0000-0001-7856-2984
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - Hecquet, Claudie
AU  - Hecquet C
AUID- ORCID: 0009-0001-2413-3794
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - Clarin, Jerry D
AU  - Clarin JD
AUID- ORCID: 0009-0008-0552-4408
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - Palma, Joann P
AU  - Palma JP
AUID- ORCID: 0009-0008-9500-5002
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - Reilly, Edward B
AU  - Reilly EB
AUID- ORCID: 0000-0003-1999-7501
AD  - AbbVie Inc., North Chicago, Illinois.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mol Cancer Ther
JT  - Molecular cancer therapeutics
JID - 101132535
RN  - 0 (Survivin)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (CD3 Complex)
RN  - 0 (Antibodies, Bispecific)
SB  - IM
MH  - Humans
MH  - T-Lymphocytes
MH  - *Carcinoma, Non-Small-Cell Lung/metabolism
MH  - Survivin/metabolism
MH  - *Lung Neoplasms/metabolism
MH  - Receptors, Antigen, T-Cell
MH  - CD3 Complex
MH  - *Leukemia, Myeloid, Acute/pathology
MH  - *Hematologic Neoplasms/metabolism
MH  - *Antibodies, Bispecific/pharmacology/therapeutic use
EDAT- 2023/06/09 19:42
MHDA- 2023/08/02 06:42
CRDT- 2023/06/09 16:52
PHST- 2022/12/01 00:00 [received]
PHST- 2023/03/17 00:00 [revised]
PHST- 2023/05/31 00:00 [accepted]
PHST- 2023/08/02 06:42 [medline]
PHST- 2023/06/09 19:42 [pubmed]
PHST- 2023/06/09 16:52 [entrez]
AID - 727246 [pii]
AID - 10.1158/1535-7163.MCT-22-0770 [doi]
PST - ppublish
SO  - Mol Cancer Ther. 2023 Aug 1;22(8):903-912. doi: 10.1158/1535-7163.MCT-22-0770.