PMID- 35212540
OWN - NLM
STAT- MEDLINE
DCOM- 20220429
LR  - 20220429
IS  - 1554-8937 (Electronic)
IS  - 1554-8929 (Linking)
VI  - 17
IP  - 3
DP  - 2022 Mar 18
TI  - Engineering Antibodies Targeting p16 MHC-Peptide Complexes.
PG  - 545-555
LID - 10.1021/acschembio.1c00808 [doi]
AB  - Senescent cells undergo a permanent cell cycle arrest and drive a host of 
      age-related pathologies. Recent transgenic mouse models indicate that removing 
      cells expressing the senescence marker p16(Ink4a) (p16) can increase median 
      lifespan and delay the onset of many aging phenotypes. However, identifying and 
      eliminating native human cells expressing p16 has remained a challenge. We 
      hypothesize that senescent cells display peptides derived from p16 in major 
      histocompatibility complex (MHC)-peptide complexes on the cell surface that could 
      serve as targetable antigens for antibody-based biologics. Using Fab-phage 
      display technology, we generated antibodies that bind to a p16 MHC-peptide 
      complex from the human leukocyte antigen (HLA) allele HLA-B*35:01. When converted 
      to single-chain Fab chimeric antigen receptor (CAR) constructs, these antibodies 
      can recognize naturally presented p16 MHC-peptide complexes on the surface of 
      cells and activate Jurkat cells. Furthermore, we developed antibodies against 
      predicted p16 MHC-peptide complexes for HLA-A*02:01 that specifically recognize 
      their respective antigen on the surface of cells. These tools establish a 
      platform to survey the surface of senescent cells and provide a potential novel 
      senolytic strategy.
FAU - Rettko, Nicholas J
AU  - Rettko NJ
AUID- ORCID: 0000-0002-4332-2697
AD  - Department of Pharmaceutical Chemistry, University of California San Francisco, 
      San Francisco, California 94158, United States.
FAU - Campisi, Judith
AU  - Campisi J
AD  - Buck Institute for Research on Aging, Novato, California 94945, United States.
AD  - Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States.
FAU - Wells, James A
AU  - Wells JA
AUID- ORCID: 0000-0001-8267-5519
AD  - Department of Pharmaceutical Chemistry, University of California San Francisco, 
      San Francisco, California 94158, United States.
AD  - Chan Zuckerberg Biohub, San Francisco, California 94158, United States.
LA  - eng
GR  - P01 AG017242/AG/NIA NIH HHS/United States
GR  - U01 AG060906/AG/NIA NIH HHS/United States
GR  - R35 GM122451/GM/NIGMS NIH HHS/United States
GR  - R01 CA248323/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20220225
PL  - United States
TA  - ACS Chem Biol
JT  - ACS chemical biology
JID - 101282906
RN  - 0 (Antibodies)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Chimeric Antigen)
SB  - IM
MH  - Animals
MH  - Antibodies
MH  - *Major Histocompatibility Complex
MH  - Mice
MH  - Mice, Transgenic
MH  - Peptides
MH  - *Receptors, Chimeric Antigen
EDAT- 2022/02/26 06:00
MHDA- 2022/04/30 06:00
CRDT- 2022/02/25 12:15
PHST- 2022/02/26 06:00 [pubmed]
PHST- 2022/04/30 06:00 [medline]
PHST- 2022/02/25 12:15 [entrez]
AID - 10.1021/acschembio.1c00808 [doi]
PST - ppublish
SO  - ACS Chem Biol. 2022 Mar 18;17(3):545-555. doi: 10.1021/acschembio.1c00808. Epub 
      2022 Feb 25.