Details

Autor(en) / Beteiligte

• Kerbauy, Lucila N
• Marin, Nancy D
• Kaplan, Mecit
• Banerjee, Pinaki P
• Berrien-Elliott, Melissa M
• Becker-Hapak, Michelle
• Basar, Rafet
• Foster, Mark
• Garcia Melo, Luciana
• Neal, Carly C
• McClain, Ethan
• Daher, May
• Nunez Cortes, Ana Karen
• Desai, Sweta
• Inng Lim, Francesca Wei
• Mendt, Mayela Carolina
• Schappe, Timothy
• Li, Li
• Shaim, Hila
• Shanley, Mayra
• Ensley, Emily L
• Uprety, Nadima
• Wong, Pamela
• Liu, Enli
• Ang, Sonny O
• Cai, Rong
• Nandivada, Vandana
• Mohanty, Vakul
• Miao, Qi
• Shen, Yifei
• Baran, Natalia
• Fowlkes, Natalie W
• Chen, Ken
• Muniz-Feliciano, Luis
• Champlin, Richard E
• Nieto, Yago L
• Koch, Joachim
• Treder, Martin
• Fischer, Wolfgang
• Okamoto, Oswaldo Keith
• Shpall, Elizabeth J
• Fehniger, Todd A
• Rezvani, Katayoun

Titel

Combining AFM13, a Bispecific CD30/CD16 Antibody, with Cytokine-Activated Blood and Cord Blood-Derived NK Cells Facilitates CAR-like Responses Against CD30 + Malignancies

Ist Teil von

• Clinical cancer research, 2021-07, Vol.27 (13), p.3744-3756

Ort / Verlag

United States

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• Natural killer (NK)-cell recognition and function against NK-resistant cancers remain substantial barriers to the broad application of NK-cell immunotherapy. Potential solutions include bispecific engagers that target NK-cell activity via an NK-activating receptor when simultaneously targeting a tumor-specific antigen, as well as enhancing functionality using IL12/15/18 cytokine pre-activation. We assessed single-cell NK-cell responses stimulated by the tetravalent bispecific antibody AFM13 that binds CD30 on leukemia/lymphoma targets and CD16A on various types of NK cells using mass cytometry and cytotoxicity assays. The combination of AFM13 and IL12/15/18 pre-activation of blood and cord blood-derived NK cells was investigated and . We found heterogeneity within AFM13-directed conventional blood NK cell (cNK) responses, as well as consistent AFM13-directed polyfunctional activation of mature NK cells across donors. NK-cell source also impacted the AFM13 response, with cNK cells from healthy donors exhibiting superior responses to those from patients with Hodgkin lymphoma. IL12/15/18-induced memory-like NK cells from peripheral blood exhibited enhanced killing of CD30 lymphoma targets directed by AFM13, compared with cNK cells. Cord-blood NK cells preactivated with IL12/15/18 and expanded with K562-based feeders also exhibited enhanced killing with AFM13 stimulation via upregulation of signaling pathways related to NK-cell effector function. AFM13-NK complex cells exhibited enhanced responses to CD30 lymphomas and . We identify AFM13 as a promising combination with cytokine-activated adult blood or cord-blood NK cells to treat CD30 hematologic malignancies, warranting clinical trials with these novel combinations.