The allogeneic TCR-enhanced Vδ2 T cell product is a novel genetically engineered cellular therapeutic. By engineering a specific BTN protein-binding moiety on its cell surface, this product harnesses the intrinsic tumoricidal potential of endogenous Vδ2 T cells and augments BTN protein recognition capability, thereby significantly boosting tumor cell killing potency. Notably, this engineered cell product exhibits no expression of co-stimulatory signaling domains and CD3ζ domains. This design circumvents T cell exhaustion triggered by overactivation and markedly enhances the in vivo persistence of therapeutic cells. This is an open, prospective, open-label Phase I/II clinical trial designed to assess the safety and therapeutic efficacy of allogeneic TCR-enhanced Vδ2 T cell injection in patients with relapsed or refractory hematologic malignancies and advanced solid tumors.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Allogeneic TCR-enhanced Vδ2 T cells in a standard 3+3 dose-escalation design. Three predefined dose levels are investigated: Dose 1: 1×10\^7 enTCR Vδ2T cells/kg, Dose 2: 3×10\^7 enTCR Vδ2T cells/kg, and Dose 3: 6×10\^7 enTCR Vδ2T cells/kg.
For patients with hematological tumors, cyclophosphamide should be administered from day 5 to day 3 before cell infusion, with a recommended dose of 500 - 1000 mg/m² per day. For patients with solid tumors, cyclophosphamide should be administered from day 4 to day 3 before cell infusion, with a recommended dose of 500 - 700 mg/m² per day.
For patients with hematological tumors, fludarabine should be administered from day 5 to day 3 before cell infusion, and the recommended dose is 30 - 50 mg/m² per day. For patients with solid tumors, fludarabine should be administered from day 4 to day 3 before cell infusion, with a recommended dose of 30 - 40 mg/m² per day.
This is only applicable to patients with solid tumors. It should be administered on the fifth day before cell infusion. The recommended dosage is 150-200 mg/m² per day.
Biotherapeutic Department of Chinsese PLA Gereral Hospital
Beijing, Beijing Municipality, China
RECRUITINGAdverse Event
AE is defined as any adverse medical event from the date of leukapheresis to 12 months after allogeneic TCR-enhanced Vδ2 T cells infusion. Among them, cytokine release syndrome (CRS), immune cell-associated neurotoxicity syndrome (ICANS) , graft-versushost disease (GVHD) are excluded . Other AEs were graded according to the regulatory agency's Medical Dictionary for Regulatory Activities (MedDRA) and common terminology criteria for adverse events (CTCAE) v5.0
Time frame: 12 months
DLTs
DLT was defined as allogeneic TCR-enhanced Vδ2 T cells-related events with onset within first 28 days following infusion
Time frame: 28 days after cell infusion
PK(Pharmacokinetics):Number and Copy Number of allogeneic TCR-enhanced Vδ2 T cell
Number and copy number of allogeneic TCR-enhanced Vδ2 T cells were assessed by number in peripheral blood.
Time frame: 12 months
PD(Pharmacodynamics):changes over time
To monitor changes over time in the cytokines mainly include interleukin-2 (IL-2 ), IL-4,IL-6, interferon-γ(IFN-γ), Tumor Necrosis Factor-alpha (TNF-α).
Time frame: 12 months
Objective Response Rate
The incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) are the response to treatment assessed by investigators.
Time frame: 12 months after cell infusion
Overall Survival(OS)
OS is defined as the time from allogeneic TCR-enhanced Vδ2 T cell infusion to the date of death.
Time frame: 12 months
Progression Free Survival (PFS)
PFS is defined as the time from the allogeneic TCR-enhanced Vδ2 T cell infusion date to the date of disease progression assessed by investigators.
Time frame: 12 months
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