Antitumor immunity induced by antibody-based natural killer cell engager therapeutics armed with not-alpha IL-2 variant

被引：56

作者：

Demaria, Olivier ^{[1
]}

Gauthier, Laurent ^{[1
]}

Vetizou, Marie ^{[1
]}

Alvarez, Audrey Blanchard ^{[1
]}

Vagne, Constance ^{[1
]}

Habif, Guillaume ^{[1
]}

Batista, Luciana ^{[1
]}

Baron, William ^{[1
]}

Belaid, Nourhene ^{[1
]}

Girard-Madoux, Mathilde ^{[1
]}

Cesari, Cedric ^{[1
]}

Caratini, Melody ^{[1
]}

Bosco, Frederic ^{[1
]}

Benac, Olivier ^{[1
]}

Lopez, Julie ^{[1
]}

Fenis, Aurore ^{[1
]}

Galluso, Justine ^{[1
]}

Trichard, Sylvia ^{[1
]}

Carrette, Barbara ^{[1
]}

Carrette, Florent ^{[1
]}

Maguer, Aurelie ^{[1
]}

Jaubert, Solene ^{[1
]}

Sansaloni, Audrey ^{[1
]}

Letay-Drouet, Robin ^{[1
]}

Kosthowa, Camille ^{[1
]}

Lovera, Naouel ^{[1
]}

Dujardin, Arnaud ^{[1
]}

Chanuc, Fabien ^{[1
]}

Le Van, Melanie ^{[1
]}

Bokobza, Sivan ^{[1
]}

Jarmuzynski, Nicolas ^{[1
]}

Fos, Camille ^{[1
]}

Gourdin, Nicolas ^{[1
]}

Remark, Romain ^{[1
]}

Lechevallier, Eric ^{[2
]}

Fakhry, Nicolas ^{[3
]}

Salas, Sebastien ^{[4
]}

Deville, Jean-Laurent ^{[5
]}

Le Grand, Roger ^{[6
,7
]}

Bonnafous, Cecile ^{[1
]}

Vollmy, Lukas ^{[1
]}

Represa, Agnes ^{[1
]}

Carpentier, Sabrina ^{[1
]}

Rossi, Benjamin ^{[1
]}

Morel, Ariane ^{[1
]}

Cornen, Stephanie ^{[1
]}

Perrot, Ivan ^{[1
]}

Morel, Yannis ^{[1
]}

Vivier, Eric ^{[1
,8
,9
]}

机构：

[1] Innate Pharma, Marseille, France

[2] Hop Conception, AP HM, Chirurg Urol & Transplantat Renale, Marseille, France

[3] Hop Conception, AP HM, ORL & Chirurg Cerv Faciale, Marseille, France

[4] CHU Timone Adulte, AP HM, Serv Oncol Med & Soins Palliatifs, Marseille, France

[5] Hop La Timone, AP HM, Oncol Med, Marseille, France

[6] Univ Paris Saclay, INSERM, CEA, Ctr Immunol Viral Auto Immune Hematol & Bacterial, Fontenay Aux Roses, France

[7] Univ Paris Saclay, INSERM, CEA, Ctr Immunol Viral Auto Immune Hematol & Bacterial, Le Kremlin Bicetre, France

[8] Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France

[9] Hop La Timone, AP HM, Marseille Immunopole, Marseille, France

来源：

CELL REPORTS MEDICINE | 2022年 / 3卷 / 10期

基金：

欧洲研究理事会;

关键词：

NK CELLS; ACTIVATION; INTERLEUKIN-2; RECEPTOR; MOUSE; IDENTIFICATION; LYMPHOCYTES; AFFINITY; IMMUNOTHERAPY; CYTOTOXICITY;

D O I：

10.1016/j.xcrm.2022.100783

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Harnessing innate immunity is emerging as a promising therapeutic approach in cancer. We report here the design of tetraspecific molecules engaging natural killer (NK) cell-activating receptors NKp46 and CD16a, the beta-chain of the interleukin-2 receptor (IL-2R), and a tumor-associated antigen (TAA). In vitro, these tetraspecific antibody-based natural killer cell engager therapeutics (ANKETs) induce a preferential activation and proliferation of NK cells, and the binding to the targeted TAA triggers NK cell cytotoxicity and cytokine and chemokine production. In vivo, tetraspecific ANKETs induce NK cell proliferation and their accumulation at the tumor bed, as well as the control of local and disseminated tumors. Treatment of non-human primates with CD20-directed tetraspecific ANKET leads to CD20(+) circulating B cell depletion, with minimal systemic cytokine release and no sign of toxicity. Tetraspecific ANKETs, thus, constitute a technological platform for harnessing NK cells as next-generation cancer immunotherapies.

引用

页数：24

共 53 条

[1] The CD3ζ adaptor structure determines functional differences between human and mouse CD16 Fc receptor signaling [J].