TY - JOUR
T1 - A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers
AU - Wong, Derek P.
AU - Roy, Nand K.
AU - Zhang, Keman
AU - Anukanth, Anusha
AU - Asthana, Abhishek
AU - Shirkey-Son, Nicole J.
AU - Dunmire, Samantha
AU - Jones, Bryan J.
AU - Lahr, Walker S.
AU - Webber, Beau R.
AU - Moriarity, Branden S.
AU - Caimi, Paolo
AU - Parameswaran, Reshmi
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - B cell-activating factor (BAFF) binds the three receptors BAFF-R, BCMA, and TACI, predominantly expressed on mature B cells. Almost all B cell cancers are reported to express at least one of these receptors. Here we develop a BAFF ligand-based chimeric antigen receptor (CAR) and generate BAFF CAR-T cells using a non-viral gene delivery method. We show that BAFF CAR-T cells bind specifically to each of the three BAFF receptors and are effective at killing multiple B cell cancers, including mantle cell lymphoma (MCL), multiple myeloma (MM), and acute lymphoblastic leukemia (ALL), in vitro and in vivo using different xenograft models. Co-culture of BAFF CAR-T cells with these tumor cells results in induction of activation marker CD69, degranulation marker CD107a, and multiple proinflammatory cytokines. In summary, we report a ligand-based BAFF CAR-T capable of binding three different receptors, minimizing the potential for antigen escape in the treatment of B cell cancers.
AB - B cell-activating factor (BAFF) binds the three receptors BAFF-R, BCMA, and TACI, predominantly expressed on mature B cells. Almost all B cell cancers are reported to express at least one of these receptors. Here we develop a BAFF ligand-based chimeric antigen receptor (CAR) and generate BAFF CAR-T cells using a non-viral gene delivery method. We show that BAFF CAR-T cells bind specifically to each of the three BAFF receptors and are effective at killing multiple B cell cancers, including mantle cell lymphoma (MCL), multiple myeloma (MM), and acute lymphoblastic leukemia (ALL), in vitro and in vivo using different xenograft models. Co-culture of BAFF CAR-T cells with these tumor cells results in induction of activation marker CD69, degranulation marker CD107a, and multiple proinflammatory cytokines. In summary, we report a ligand-based BAFF CAR-T capable of binding three different receptors, minimizing the potential for antigen escape in the treatment of B cell cancers.
UR - http://www.scopus.com/inward/record.url?scp=85122793323&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85122793323&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-27853-w
DO - 10.1038/s41467-021-27853-w
M3 - Article
C2 - 35017485
AN - SCOPUS:85122793323
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 217
ER -
