A Novel Bi-Specific T-Cell Engager Targeting ILT3 Is Potently Effective in Multiple Myeloma

Meo, Francesco; Iyer, Anjushree; Akama, Keith; Yu, Christina Y.; Cheng, Rujin; Cesarano, Annamaria; Marino, Silvia; Aljoufi, Arafat; Soni, Rajesh Kumar; Roda, Julie M.; Sissons, James; Vu, Ly; Guzmán, Mónica L.; Huang, Kun; Roodman, David; Perna, Fabiana

doi:10.1182/blood-2022-167584

Cited by 2 publications

(1 citation statement)

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“…A potential novel target for targeted therapy in MM is immunoglobulin-like transcript 3 (ILT3), which is an immunoreceptor tyrosine-based inhibition motif-containing receptor, with high expression on MM cells and low or absent expression in normal tissues [ 73 ]. A CD3xILT3 BsAb showed promising anti-MM activity in preclinical experiments [ 73 ].…”

Section: Other Targets For T-cell Redirecting Bispecific Antibodiesmentioning

confidence: 99%

T-cell redirecting bispecific and trispecific antibodies in multiple myeloma beyond BCMA

van de Donk,

O’Neill,

de Ruijter

et al. 2023

Current Opinion in Oncology

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Purpose of review B-cell maturation antigen (BCMA)-directed T-cell immunotherapies, such as chimeric antigen receptor T-cells (CAR T-cells) and bispecific antibodies (BsAbs) have markedly improved the survival of triple-class refractory multiple myeloma (MM). However, the majority of patients still develops disease progression, underlining the need for new agents for these patients. Recent findings Novel T-cell redirecting BsAbs targeting alternative tumor-associated antigens have shown great promise in heavily pretreated MM, including patients previously exposed to BCMA-directed therapies. This includes the G-protein-coupled receptor class 5 member D (GPRC5D)-targeting BsAbs talquetamab and forimtamig, as well as the Fc receptor-homolog 5 (FcRH5)-targeting BsAb cevostamab. Toxicity associated with these BsAbs includes cytokine-release syndrome, cytopenias, and infections. In addition, GPRC5D-targeting BsAbs are associated with specific ‘on target/off tumor’ toxicities including rash, nail disorders, and dysgeusia. Trispecifc antibodies targeting two different MM-associated antigens to prevent antigen escape are in early clinical development, as well as trispecific antibodies (TsAbs) that provide an additional co-stimulatory signal to T-cells to prevent their exhaustion. Summary Various T-cell redirecting BsAbs are in advanced stages of clinical development with promising activity and a manageable toxicity profile. Ongoing studies are evaluating combination strategies, fixed-duration treatment, and use of BsAbs in earlier lines of therapy. TsAbs hold great promise for the future.

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Section: Other Targets For T-cell Redirecting Bispecific Antibodiesmentioning

confidence: 99%

T-cell redirecting bispecific and trispecific antibodies in multiple myeloma beyond BCMA

van de Donk,

O’Neill,

de Ruijter

et al. 2023

Current Opinion in Oncology

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Bispecific antibody targets and therapies in multiple myeloma

Rees,

Abdallah,

Yohannan

et al. 2024

Front. Immunol.

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Recently, several bispecific antibodies (BsAbs) have been approved for the treatment of relapsed multiple myeloma (MM) after early phase trials in heavily pre-treated patients demonstrated high response rates and impressive progression-free survival with monotherapy. These BsAbs provide crucial treatment options for relapsed patients and challenging decisions for clinicians. Evidence on the optimal patient population, treatment sequence, and duration of these therapeutics is unknown and subject to active investigation. While rates of cytokine release syndrome and neurotoxicity appear to be lower with BsAbs than with CAR T-cells, morbidity from infection is high and novel pathways of treatment resistance arise from the longitudinal selection pressure of chronic BsAb therapy. Lastly, a wealth of novel T-cell engagers with unique antibody-structures and antigenic targets are under active investigation with promising early outcome data. In this review, we examine the mechanism of action, therapeutic targets, combinational approaches, sequencing and mechanisms of disease relapse for BsAbs in MM.

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A Novel Bi-Specific T-Cell Engager Targeting ILT3 Is Potently Effective in Multiple Myeloma

Cited by 2 publications

References 0 publications

T-cell redirecting bispecific and trispecific antibodies in multiple myeloma beyond BCMA

T-cell redirecting bispecific and trispecific antibodies in multiple myeloma beyond BCMA

Bispecific antibody targets and therapies in multiple myeloma

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