Delving into the Latest Updates on TSA-T directed against proteogenomically determined personalized TSA(Children's National Research Institute) with Synapse

Overview

Basic Info

Drug Type

T-lymphocyte cell therapy

Synonyms

Multi-tumor antigen specific cytotoxic T lymphocytes (TSA-T) directed against proteogenomically determined personalized tumor-specific antigens (TSA)

Target-

Action

stimulants

Mechanism

Immunostimulants

Therapeutic Areas

NeoplasmsNervous System DiseasesOther Diseases

Active Indication

childhood CNS embryonal tumorEpendymoblastomaPineoblastoma+ [5]

Inactive Indication-

Originator Organization

Children's National Research Institute

Active Organization

Children's National Research Institute

Inactive Organization-

License Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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This is an open-label phase 1 safety and feasibility study that will employ multi-tumor antigen specific cytotoxic T lymphocytes (TSA-T) directed against proteogenomically determined personalized tumor-specific antigens (TSA) derived from a patient's primary brain tumor tissues. Young patients with embryonal central nervous system (CNS) malignancies typically are unable to receive irradiation due to significant adverse effects and are treated with intensive chemotherapy followed by autologous stem cell rescue; however, despite intensive therapy, many of these patients relapse. In this study, individualized TSA-T cells will be generated against proteogenomically determined tumor-specific antigens after standard of care treatment in children less than 5 years of age with embryonal brain tumors. Correlative biological studies will measure clinical anti-tumor, immunological and biomarker effects.

Start Date20 Sep 2024

Sponsor / Collaborator

Children's National Research Institute

NCT03652545

/ Active, not recruitingPhase 1IIT

Phase I REsearch on Multi-antigen T Cell Infusion Against Neuro-oncologic Disease

This Phase I dose-escalation trial is designed to determine the safety and feasibility of rapidly generated tumor multi-antigen associated specific cytotoxic T lymphocytes (TAA-T) in patients with newly diagnosed diffuse intrinsic pontine gliomas DIPGs (Group A) or recurrent, progressive, or refractory non-brainstem CNS malignancies (Group B).
Pediatric and adult patients who have high-risk CNS tumors known to typically have positivity for one or more Tumor Antigen Associated (TAA) (WT1, PRAME and/or Survivin) will be eligible. TAA-T will all be generated from patient peripheral blood mononuclear cells (PBMC).
Group A patients (DIPG): The first TAA-T dose will be infused any time 14 days or more after completion of radiotherapy.
Group B patients (other recurrent/progressive/refractory CNS tumors): The first TAA-T dose will be infused any time 14 days or more after completing most recent course of conventional (non-investigational) therapy for their disease AND after appropriate washout periods as detailed in eligibility criteria.

Start Date12 Dec 2018

Sponsor / Collaborator

Children's National Research Institute

[+1]

100 Clinical Results associated with TSA-T directed against proteogenomically determined personalized TSA(Children's National Research Institute)

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100 Translational Medicine associated with TSA-T directed against proteogenomically determined personalized TSA(Children's National Research Institute)

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100 Patents (Medical) associated with TSA-T directed against proteogenomically determined personalized TSA(Children's National Research Institute)

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2

Literatures (Medical) associated with TSA-T directed against proteogenomically determined personalized TSA(Children's National Research Institute)

26 Apr 2022·Blood AdvancesQ2 · MEDICINE

Outcome of donor-derived TAA-T cell therapy in patients with high-risk or relapsed acute leukemia post allogeneic BMT

Q2 · MEDICINE

Article

Author: Stanojevic, Maja ; Cruz, C. Russell ; Jones, Richard J. ; Dave, Hema ; Bollard, Catherine M. ; Fulton, Kenneth ; Keller, Michael ; Zhang, Anqing ; Jacobsohn, David ; Zhang, Nan ; Barrett, A. John ; Datar, Anushree ; Tanna, Jay ; Hanley, Patrick J. ; Dome, Jeffrey S. ; Liang, Hua ; Kinoshita, Hannah ; Cooke, Kenneth R. ; Fortiz, Maria Fernanda ; Hoq, Fahmida ; Kukadiya, Divyesh ; Lang, Haili ; Shibli, Abeer ; Williams, Kirsten M. ; Grant, Melanie

AbstractPatients with hematologic malignancies relapsing after allogeneic blood or marrow transplantation (BMT) have limited response to conventional salvage therapies, with an expected 1-year overall survival (OS) of <20%. We evaluated the safety and clinical outcomes following administration of a novel T-cell therapeutic targeting 3 tumor-associated antigens (TAA-T) in patients with acute leukemia who relapsed or were at high risk of relapse after allogeneic BMT. Lymphocytes obtained from the BMT donor were manufactured to target TAAs WT1, PRAME, and survivin, which are over-expressed and immunogenic in most hematologic malignancies. Patients received TAA-T infusions at doses of 0.5 to 4 × 107/m2. Twenty-three BMT recipients with relapsed/refractory (n = 11) and/or high-risk (n = 12) acute myeloid leukemia (n = 20) and acute lymphoblastic leukemia (n = 3) were infused posttransplant. No patient developed cytokine-release syndrome or neurotoxicity, and only 1 patient developed grade 3 graft-versus-host disease. Of the patients who relapsed post-BMT and received bridging therapy, the majority (n = 9/11) achieved complete hematologic remission before receiving TAA-T. Relapsed patients exhibited a 1-year OS of 36% and 1-year leukemia-free survival of 27.3% post–TAA-T. The poorest prognosis patients (relapsed <6 months after transplant) exhibited a 1-year OS of 42.8% postrelapse (n = 7). Median survival was not reached for high-risk patients who received preemptive TAA-T posttransplant (n = 12). Although as a phase 1 study, concomitant antileukemic therapy was allowed, TAA-T were safe and well tolerated, and sustained remissions in high-risk and relapsed patients were observed. Moreover, adoptively transferred TAA-T detected by T-cell receptor V-β sequencing persisted up to at least 1 year postinfusion. This trial was registered at clinicaltrials.gov as #NCT02203903.

10 Sep 2019·Journal of Clinical OncologyQ1 · MEDICINE

Immunotherapy of Relapsed and Refractory Solid Tumors With Ex Vivo Expanded Multi-Tumor Associated Antigen Specific Cytotoxic T Lymphocytes: A Phase I Study

Q1 · MEDICINE

Article

Author: Banerjee, Payal ; Darko, Sam ; Panchapakesan, Karuna ; Meany, Holly J. ; O’Brien, Barbara ; Bollard, Catherine M. ; Lang, Haili ; Hoq, Fahmida ; Datar, Anushree ; Hanley, Patrick J. ; Fortiz, Maria Fernanda ; Wang, Yunfei ; Dome, Jeffrey S. ; Ulrey, Robert ; Stanojevic, Maja ; Albihani, Shuroug ; Hanajiri, Ryo ; Saunders, Devin ; Cruz, C. Russell ; Hont, Amy B.

PURPOSE Tumor-associated antigen cytotoxic T cells (TAA-Ts) represent a new, potentially effective and nontoxic therapeutic approach for patients with relapsed or refractory solid tumors. In this first-in-human trial, we investigated the safety of administering TAA-Ts that target Wilms tumor gene 1, preferentially expressed antigen of melanoma, and survivin to patients with relapsed/refractory solid tumors. MATERIALS AND METHODS TAA-T products were generated from autologous peripheral blood and infused over three dose levels: 1, 2, and 4 × 107 cells/m2. Patients were eligible for up to eight infusions administered 4 to 7 weeks apart. We assessed dose limiting toxicity during the first 45 days after infusion. Disease response was determined within the context of a phase I trial. RESULTS There were no dose-limiting toxicities. Of 15 evaluable patients, 11 (73%) with stable disease or better at day 45 postinfusion were defined as responders. Six responders remain without progression at a median of 13.9 months (range, 4.1 to 19.9 months) after initial TAA-Ts. Patients who were treated at the highest dose level showed the best clinical outcomes, with a 6-month progression-free survival of 73% after TAA-T infusion compared with a 38% 6-month progression-free survival with prior therapy. Antigen spreading and a reduction in circulating tumor-associated antigens using digital droplet polymerase chain reaction was observed in patients after TAA-T infusion. CONCLUSION TAA-Ts safely induced disease stabilization, prolonged time to progression, and were associated with antigen spreading and a reduction in circulating tumor-associated antigen DNA levels in patients with relapsed/refractory solid tumors without lymphodepleting chemotherapy before infusion. TAA-Ts are a promising new treatment approach for patients with solid tumors.

100 Deals associated with TSA-T directed against proteogenomically determined personalized TSA(Children's National Research Institute)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
childhood CNS embryonal tumor	Phase 1	United States	Children's National Research Institute	20 Sep 2024
Ependymoblastoma	Phase 1	United States	Children's National Research Institute	20 Sep 2024
Pineoblastoma	Phase 1	United States	Children's National Research Institute	20 Sep 2024
Rhabdoid Tumor of the CNS	Phase 1	United States	Children's National Research Institute	20 Sep 2024
Diffuse Intrinsic Pontine Glioma	Phase 1	United States	Children's National Research Institute	12 Dec 2018
Ependymoma	Phase 1	United States	Children's National Research Institute	12 Dec 2018
High grade glioma	Phase 1	United States	Children's National Research Institute	12 Dec 2018
Medulloblastoma	Phase 1	United States	Children's National Research Institute	12 Dec 2018