Delving into the Latest Updates on HX-t001 with Synapse

Overview

Basic Info

Drug Type

TCR therapy

Synonyms

CMV (T cell Receptor) T cell therapy China Immunotech, CMV TCR T cell therapy (China Immunotech)

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Target-

Mechanism

Gene transference, T lymphocyte replacements

Therapeutic Areas

Infectious DiseasesOther Diseases

Active Indication

Cytomegalovirus InfectionsCytomegalovirus viremia

Inactive Indication-

Originator Organization

BriSTAR Immunotech LimitedStartup

Active Organization

BriSTAR Immunotech LimitedStartup

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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BackgroundCytomegalovirus (CMV) reactivation after unmanipulated haploidentical stem cell transplantation (SCT) frequently occurs, causing life-threatening morbidities and transplantation failure. Pre-emptive therapy upon the detection of CMV viremia using antiviral agents is currently the standard of care but it was associated with significant toxicity. The CMV antigen-specific cytotoxic T lymphocyte therapy was limited by the time-consuming manufacture process and relatively low success rate. More effective and safer approaches for the treatment of CMV reactivation after haploidentical SCT are in urgent need.MethodsA single-arm, open-label, phase I clinical trial evaluating the safety and efficacy of CMV-targeting T cell receptor-engineered T (CMV-TCR-T) cell therapy as the first-line pre-emptive therapy for patients with CMV reactivation after haploidentical peripheral blood SCT (PBSCT) was conducted in the Chinese PLA General Hospital. Six patients with CMV reactivation after haploidentical SCT were adoptively transferred by one to three doses of SCT donors-derived CMV-TCR-T cells. This trial was a dose-escalation study with doses ranging from 1×103CMV-TCR-T cells/kg body weight per dose to 5×105CMV-TCR-T cells/kg per dose.ResultsExcept for the grade 1 cytokine release syndrome observed in one patient and mild fever in two patients, no other adverse events were observed. Four patients had response within a month after CMV-TCR-T cell infusion without the administration of any antiviral agents. The other two patients who initially did not respond to CMV-TCR-T cell therapy had salvage ganciclovir and foscarnet administration and then had rapid CMV clearance. The CMV-TCR-T cells displayed overall robust expansion and persistence in the peripheral blood after infusion. The CMV-TCR-T cells were first detected in the peripheral blood of these patients 3–7 days after the first dose of CMV-TCR-T infusion, rapidly expanded and persisted for at least 1–4 months, providing long-term protection against CMV reactivation. In one patient, the CMV-TCR-T cells started to expand even when the anti-graft-versus-host disease reagents were still being used, further indicating the proliferation potential of CMV-TCR-T cells.ConclusionsOur study first showed CMV-TCR-T cell as a highly feasible, safe and effective first-line pre-emptive treatment for CMV reactivation after haploidentical PBSCT.Trial registration numberClinicalTrials.gov Registry (NCT05140187).

npj Vaccines

Highly stable and immunogenic CMV T cell vaccine candidate developed using a synthetic MVA platform

Article

Author: Diamond, Don J ; Kha, Mindy ; Wussow, Felix ; Martinez, Joy ; Dempsey, Shannon ; Kim, Taehyun ; Chiuppesi, Flavia ; Park, Yoonsuh ; Nguyen, Vu H ; Medrano, Leonard ; Iniguez, Angelina ; Kaltcheva, Teodora ; Yll-Pico, Marcal

AbstractHuman cytomegalovirus (CMV) is the most common infectious cause of complications post-transplantation, while a CMV vaccine for transplant recipients has yet to be licensed. Triplex, a multiantigen Modified Vaccinia Ankara (MVA)-vectored CMV vaccine candidate based on the immunodominant antigens phosphoprotein 65 (pp65) and immediate-early 1 and 2 (IE1/2), is in an advanced stage of clinical development. However, its limited genetic and expression stability restricts its potential for large-scale production. Using a recently developed fully synthetic MVA (sMVA) platform, we developed a new generation Triplex vaccine candidate, T10-F10, with different sequence modifications for enhanced vaccine stability. T10-F10 demonstrated genetic and expression stability during extensive virus passaging. In addition, we show that T10-F10 confers comparable immunogenicity to the original Triplex vaccine to elicit antigen-specific T cell responses in HLA-transgenic mice. These results demonstrate improvements in translational vaccine properties of an sMVA-based CMV vaccine candidate designed as a therapeutic treatment for transplant recipients.

100 Deals associated with HX-t001

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Cytomegalovirus Infections	Phase 1	CN	BriSTAR Immunotech LimitedStartup	19 Dec 2019
Cytomegalovirus viremia	Preclinical	CN	BriSTAR Immunotech LimitedStartup	30 Jan 2022

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04153279 (Pubmed) Manual	Phase 1	Cytomegalovirus Infections	7	pp65-specific TCR-T cell therapy	(ybcgdhzkyq) = zildixgyhe zpdeyygidb (vbirfawmfx ) View more	Positive	28 Aug 2022