Natural killer receptor (NKR) expression may offer a useful diagnostic marker, and potential therapeutic target, among patients with acute adult T-cell leukemia (ATL), according to research published in Blood.

ATL is caused by infection with the human T-cell leukemia virus type 1 (HTLV-1). Although patients with any of the ATL subtypes may present with a range of symptoms, each, such as smoldering or chronic ATL, is treated differently.

Previous research into ATL has suggested that NRK expression may play a role in disease etiology and progression. KIR3DL2 (CD158K), a killer immunoglobulin-like receptor, is usually expressed by NK cells; research has suggested, furthermore, that some patients with ATL may have circulating tumor cells expressing KIR3DL2.


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For this study (ClinicalTrials.gov Identifier: NCT02593045), researchers evaluated NKR expression — and in particular, KIR3DL2 expression — among patients with acute ATL. They also investigated whether lacutamab, a cytotoxic monoclonal antibody that targets KIR3DL2, may be effective at eliminating primary ATL cells.

Data and samples from 92 patients with ATL were included. This included a discovery cohort of 21 patients to determine NKR expression in the following receptors: KIR2DL1/2DS1, KIR2DL2/2DL3/2DS2, KIR3DL2, NKG2A, NKG2C, and NKp46. The overall cohort also included 71 patients in whom KIR3DL2 levels were evaluated.

Analysis showed that, of the NKRs evaluated, only KIR3DL2 was expressed in samples from patients with acute ATL, compared with either lymphoma or chronic/smoldering ATL (P =.001).

Using PrimeFlow RNA testing, the authors also showed that both TAX messenger RNA and KIR3DL2 levels were correlated on ATL cells in CD41 T cells infected with HTLV-1. Furthermore, HTLV-1 infection appeared to trigger KIR3DL2 by CD41 T cells.

Lacutamab appeared to selectively kill KIR3DL2 primary ATL cells in an ex vivo setting. The authors noted that they are conducting a phase 2 study evaluating the safety and efficacy of lacutamab, which will include patients with acute ATL.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Cheminant M, Lhermitte L, Bruneau J, et al. KIR3DL2 contributes to the typing of acute adult T-cell leukemia and is a potential therapeutic target. Blood. 2022;140(13):1522-1532. doi:10.1182/blood.2022016765