Delving into the Latest Updates on Anti-CD3/anti-EGFR -activated T cells(Barbara Ann Karmanos Cancer Institute) with Synapse

Overview

Basic Info

Drug Type

Bispecific T-cell Engager (BiTE)

Synonyms

EGFR BATs, EGFRBi-Armed Autologous T Cells(Barbara Ann Karmanos Cancer Institute), anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) armed activated T cells

Target

CD3 x EGFR

Mechanism

CD3 modulators(T cell surface glycoprotein CD3 modulators), EGFR modulators(Epidermal growth factor receptor erbB1 modulators)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease

Active Indication

Pancreatic Cancer

Inactive Indication

GliosarcomaMalignant neoplasm of large intestineRecurrent Colon Cancer+ [1]

Originator Organization

Barbara Ann Karmanos Cancer Institute

Active Organization

Barbara Ann Karmanos Cancer Institute

University of Virginia Foundation

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

Login to view timeline

This protocol will confirm toxicities and estimate the clinical efficacy of combining anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) armed activated T cells (EGFR BATs) given to patients with locally advanced or metastatic pancreatic cancer who have received at least one dose of first line chemotherapy and may have responding, stable or progressive disease. Phase Ib will confirm a safe dose of 8 infusions, given twice weekly, of EGFR-BATs in 3 to 6 subjects. The phase II portion of the trial will test the clinical efficacy of this dose in 22 patients (including those in Phase Ib).

Start Date28 Jul 2017

Sponsor / Collaborator

University of Virginia

NCT01420874 / CompletedPhase 1IIT

Treatment of Advanced Colorectal or Pancreatic Cancer With Anti-CD3 x Anti-EGFR-Armed Activated T-Cells (Phase Ib)

The purpose of this research study is for the participant to give their own T cells (a type of blood cell in the body that can fight infections and possibly cancer) to them after they have been removed, grown in a lab, and then coated with an experimental drug.
This study will determine the highest dose of EGFR2Bi coated T cells that can be given without causing severe side effects. Initially a group of 3 participants will receive the same dose of study drug. If no serious side effects occur, the next group of participants will receive a slightly higher dose of study agent. The following groups of participants will receive higher doses of the study drug until a dose is reached where there are unacceptable side effects and maximum tolerated dose is found, or the planned highest dose level is reached with no side effects.

Start Date17 Aug 2011

Sponsor / Collaborator

Barbara Ann Karmanos Cancer Institute

100 Clinical Results associated with Anti-CD3/anti-EGFR -activated T cells(Barbara Ann Karmanos Cancer Institute)

Login to view more data

100 Translational Medicine associated with Anti-CD3/anti-EGFR -activated T cells(Barbara Ann Karmanos Cancer Institute)

Login to view more data

100 Patents (Medical) associated with Anti-CD3/anti-EGFR -activated T cells(Barbara Ann Karmanos Cancer Institute)

Login to view more data

61

Literatures (Medical) associated with Anti-CD3/anti-EGFR -activated T cells(Barbara Ann Karmanos Cancer Institute)

01 Jan 2024·Journal of Neuro-Oncology

Phase I study targeting newly diagnosed grade 4 astrocytoma with bispecific antibody armed T cells (EGFR BATs) in combination with radiation and temozolomide

Article

Author: Lopes, M Beatriz ; Kassay-McAllister, Jessica ; Schiff, David ; Fadul, Camilo E ; Le, Tri ; Donahue, Joseph ; Lum, Lawrence G ; Schalk, Dana ; Thakur, Archana ; Kim, Jungeun ; Purow, Benjamin ; Dillon, Patrick ; Liu, Qin

AbstractPurposeThe purpose of this study was to determine the safety, feasibility, and immunologic responses of treating grade 4 astrocytomas with multiple infusions of anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) armed T cells (EGFR BATs) in combination with radiation and chemotherapy.MethodsThis phase I study used a 3 + 3 dose escalation design to test the safety and feasibility of intravenously infused EGFR BATs in combination with radiation and temozolomide (TMZ) in patients with newly diagnosed grade 4 astrocytomas (AG4). After finding the feasible dose, an expansion cohort with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) tumors received weekly EGFR BATs without TMZ.ResultsThe highest feasible dose was 80 × 109 EGFR BATs without dose-limiting toxicities (DLTs) in seven patients. We could not escalate the dose because of the limited T-cell expansion. There were no DLTs in the additional cohort of three patients with unmethylated MGMT tumors who received eight weekly infusions of EGFR BATs without TMZ. EGFR BATs infusions induced increases in glioma specific anti-tumor cytotoxicity by peripheral blood mononuclear cells (p < 0.03) and NK cell activity (p < 0.002) ex vivo, and increased serum concentrations of IFN-γ (p < 0.03), IL-2 (p < 0.007), and GM-CSF (p < 0.009).ConclusionTargeting AG4 with EGFR BATs at the maximum feasible dose of 80 × 109, with or without TMZ was safe and induced significant anti-tumor-specific immune responses. These results support further clinical trials to examine the efficacy of this adoptive cell therapy in patients with MGMT-unmethylated GBM.ClinicalTrials.gov Identifier: NCT03344250

01 Sep 2023·Molecular Therapy - Nucleic Acids

Targeting oncogenic KRAS in non-small cell lung cancer with EGFR aptamer-conjugated multifunctional RNA nanoparticles

Article

Author: Guo, Peixuan ; Binzel, Daniel W ; Li, Zhefeng ; Williams, Terence M ; Yang, Linlin

KRAS mutations are one of the most common oncogenic driver mutations in human cancers, including non-small cell lung cancer (NSCLC), and have established roles in cancer pathogenesis and therapeutic resistance. The development of effective inhibitors of mutant KRAS represents a significant challenge. Three-way junction (3WJ)-based multi-functional RNA nanoparticles have the potential to serve as an effective in vivo siRNA delivery platform with the ability to enhance tumor targeting specificity and visualize biodistribution through an imaging moiety. Herein, we assembled novel EGFR_apt-3WJ-siKRAS^G12C mutation targeted nanoparticles to target EGFR-expressing human NSCLC harboring a KRAS^G12C mutation to silence KRAS^G12C expression in a tumor cell-specific fashion. We found that EGFR_apt-3WJ-siKRAS^G12C nanoparticles potently depleted cellular KRAS^G12C expression, resulting in attenuation of downstream MAPK pathway signaling, cell proliferation, migration/invasion ability, and sensitized NSCLC cells to chemoradiotherapy. In vivo, these nanoparticles induced tumor growth inhibition in KRAS^G12C NSCLC tumor xenografts. Together, this study suggests that the 3WJ pRNA-based platform has the potential to suppress mutant KRAS activity for the treatment of KRAS-driven human cancers, and warrants further development for clinical translation.

01 Apr 2022·Colloids and Surfaces B: BiointerfacesQ2 · ENGINEERING & TECHNOLOGY

Targeted delivery of cancer drug paclitaxel to chordomas tumor cells via an RNA nanoparticle harboring an EGFR aptamer

Q2 · ENGINEERING & TECHNOLOGY

Article

Author: Xiao, Dan ; Zhuang, Jianxiong ; Wang, Yi ; Huang, Yongxiong ; Chen, P ; Zhang, Lei ; Huang, Shuaihao

Paclitaxel has been extensively used in clinics for cancer treatment. However, its limited solubility in aqueous solution and high occurrence of side effects have also been widely reported. In this study, we constructed a biocompatible RNA nanoparticle delivery system (3WJ-EGFR_apt) that includes 3WJ (3-way junction) nanoparticle with a size of 4.85 ± 0.59 nm as a backbone and an EGFR (epidermal growth factor receptor) aptamer for specific targeting to chordomas cells, which owns the encapsulation ability of drug paclitaxel (PTX) for cancer therapy. Confocal microscopy and flow cytometry results confirmed 3WJ-EGFR_apt nanoparticle exhibited excellent specific targeting to chordomas cell U-CH2 which is an EGFR(+) cell line; while the 3WJ nanoparticle lose the targeted ability. Both of the two nanoparticles own no sensitivity to lung cancer cell H520 which is an EGFR(-) cell line. Moreover, the 3WJ-EGFR_apt nanoparticle encapsulated drug PTX could enhance the inhibition efficiency of chordomas tumor cells U-CH2 as compared to free PTX alone. This work demonstrates that RNA-3WJ constructed with a targeting aptamer provides a compromising targeted drug delivery ability on chordomas cells for therapeutics.

100 Deals associated with Anti-CD3/anti-EGFR -activated T cells(Barbara Ann Karmanos Cancer Institute)

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Pancreatic Cancer	Phase 2	-	Barbara Ann Karmanos Cancer Institute	-
Pancreatic Cancer	Phase 2	-	University of Virginia Foundation	-
Gliosarcoma	Preclinical	-	Barbara Ann Karmanos Cancer Institute	01 Aug 2015
Recurrent Glioblastoma	Preclinical	-	Barbara Ann Karmanos Cancer Institute	01 Aug 2015
Malignant neoplasm of large intestine	Preclinical	US	Barbara Ann Karmanos Cancer Institute	17 Aug 2011
Recurrent Colon Cancer	Preclinical	US	Barbara Ann Karmanos Cancer Institute	17 Aug 2011

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01420874 \| NCT02620865 (Pubmed \| Oncoimmunology) Manual	Phase 1/2	Pancreatic Cancer	7	anti-CD3 x anti-EGFR bispecific antibody	(pmddvcqtlr) = rzuzlypaos ecakjxmkdb (ilfbkxuvih ) View more	Positive	10 Jun 2020
AACR2016	Not Applicable	Head and Neck Neoplasms	63	Cetuximab-based therapy + high ADCC + EGFR 3+ status	amontpujdi(faktyvtgmo) = Median ADCC response at treatment start for all patients was 56.1% (range 5-99%) hppxkmpwys (ocivttacql )	Positive	15 Jul 2016
AACR2016	Not Applicable	Head and Neck Neoplasms	63	Cetuximab-based therapy + low ADCC + EGFR 3+ status		Positive	15 Jul 2016
ASCO2012	Phase 1	Solid tumor \| Recurrent Non-Small Cell Lung Cancer	6	Anti-CD3 x anti-EGFR bispecific antibody (EGFRBi)	ssszwhakgq(oyugslgtgh) = grade 2= 1 pt, grade 3= 1 pt uzcyxgbkhi (nelxrewxpb ) View more	-	20 May 2012