Phenotypic and functional characterization of posoleucel, a multivirus-specific T cell therapy for the treatment and prevention of viral infections in immunocompromised patients

Spyridoula Vasileiou; Manik Kuvalekar; Yovana Velazquez; Ayumi Watanabe; Ann M Leen; Sarah A Gilmore

doi:10.1016/j.jcyt.2024.03.012

Phenotypic and functional characterization of posoleucel, a multivirus-specific T cell therapy for the treatment and prevention of viral infections in immunocompromised patients

Cytotherapy. 2024 Mar 19:S1465-3249(24)00100-2. doi: 10.1016/j.jcyt.2024.03.012. Online ahead of print.

Authors

Spyridoula Vasileiou¹, Manik Kuvalekar¹, Yovana Velazquez¹, Ayumi Watanabe², Ann M Leen¹, Sarah A Gilmore³

Affiliations

¹ Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX; AlloVir, Inc., Waltham, MA.
² Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX.
³ AlloVir, Inc., Waltham, MA. Electronic address: sgilmore@allovir.com.

PMID: 38597860
DOI: 10.1016/j.jcyt.2024.03.012

Abstract

Background: Deficits in T cell immunity translate into increased risk of severe viral infection in recipients of solid organ and hematopoietic cell transplants. Thus, therapeutic strategies that employ the adoptive transfer of virus-specific T cells are being clinically investigated to treat and prevent viral diseases in these highly immunocompromised patients. Posoleucel is an off-the-shelf multivirus-specific T cell investigational product for the treatment and prevention of infections due to adenovirus, BK virus, cytomegalovirus, Epstein-Barr virus, human herpesvirus 6 or JC virus.

Methods: Herein we perform extensive characterization of the phenotype and functional profile of posoleucel to illustrate the cellular properties that may contribute to its in vivo activity.

Results and conclusions: Our results demonstrate that posoleucel is enriched for central and effector memory CD4⁺ and CD8⁺ T cells with specificity for posoleucel target viruses and expressing a broad repertoire of T cell receptors. Antigen-driven upregulation of cell-surface molecules and production of cytokine and effector molecules indicative of proliferation, co-stimulation, and cytolytic potential demonstrate the specificity of posoleucel and its potential to mount a broad, polyfunctional, and effective Th1-polarized antiviral response upon viral exposure. We also show the low risk for off-target and nonspecific effects as evidenced by the enrichment of posoleucel in memory T cells, low frequency of naive T cells, and lack of demonstrated alloreactivity in vitro. The efficacy of posoleucel is being explored in four placebo-controlled clinical trials in transplant recipients to treat and prevent viral infections (NCT05179057, NCT05305040, NCT04390113, NCT04605484).

Keywords: hematopoietic cell transplant; immunotherapy; infectious disease; solid organ transplant; virus-specific T cell therapy.

Associated data

ClinicalTrials.gov/NCT04605484
ClinicalTrials.gov/NCT04390113
ClinicalTrials.gov/NCT05305040
ClinicalTrials.gov/NCT05179057