The Novel Bispecific Innate Cell Engager (ICE®) AFM28 Efficiently Directs Allogeneic NK Cells to CD123+ Leukemic Stem- and Progenitor Cells in AML

Schmitt, Nanni; Siegler, Jana-Julia; Wagner, Lena; Schulze, Nicole; Beck, A.; Hofmann, Wolf‐Karsten; Haneke, Torsten; Reusch, Uwe; Medina-Echeverz, José; Endell, Jan; Ross, Thorsten; Merz, Christian J.; Nowak, Daniel

doi:10.1182/blood-2022-169729

Cited by 2 publications

(1 citation statement)

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“…AFM28 is a tetravalent anti-CD123 NKCE BsAb which also belongs to the ROCK platform, with a totally different format: a Fc-silent mAb directed against CD123 with scFv anti-CD16 appended at the C-terminal end of both heavy chains. In vitro results in a panel of AML cell lines showed effective ADCC against CD123 + cells by allogeneic NK cells and independent blocking of IL-3R signaling [ 118 ]. A phase I clinical trial has just been launched in patients with AML (NCT05817058).…”

Section: Nk Cells Engagersmentioning

confidence: 99%

Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies

Tapia-Galisteo,

Álvarez-Vallina,

Sanz

2023

J Hematol Oncol

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Immune cell engagers are engineered antibodies with at least one arm binding a tumor-associated antigen and at least another one directed against an activating receptor in immune effector cells: CD3 for recruitment of T cells and CD16a for NK cells. The first T cell engager (the anti-CD19 blinatumomab) was approved by the FDA in 2014, but no other one hit the market until 2022. Now the field is gaining momentum, with three approvals in 2022 and 2023 (as of May): the anti-CD20 × anti-CD3 mosunetuzumab and epcoritamab and the anti-B cell maturation antigen (BCMA) × anti-CD3 teclistamab, and another three molecules in regulatory review. T cell engagers will likely revolutionize the treatment of hematological malignancies in the short term, as they are considerably more potent than conventional monoclonal antibodies recognizing the same tumor antigens. The field is thriving, with a plethora of different formats and targets, and around 100 bispecific T cell engagers more are already in clinical trials. Bispecific NK cell engagers are also in early-stage clinical studies and may offer similar efficacy with milder side effects. Trispecific antibodies (engaging either T cell or NK cell receptors) raise the game even further with a third binding moiety, which allows either the targeting of an additional tumor-associated antigen to increase specificity and avoid immune escape or the targeting of additional costimulatory receptors on the immune cell to improve its effector functions. Altogether, these engineered molecules may change the paradigm of treatment for relapsed or refractory hematological malignancies.

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Section: Nk Cells Engagersmentioning

confidence: 99%