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

Action

stimulants, modulators

Mechanism

CD3 stimulants(T cell surface glycoprotein CD3 stimulants), 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-

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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

NCT02521090

/ WithdrawnPhase 1/2IIT

Targeting Recurrent Glioblastoma With Anti-CD3 x Anti-EGFR Bispecific Antibody Armed T Cells: A Phase I/II Study

This phase I/II trial studies the side effects and best dose of epidermal growth factor receptor bispecific antibody (EGFRBi)-armed autologous T cells and how well it works in treating patients with glioblastoma that have come back or does not respond to treatment. EGFRBi-armed autologous T cells coated with antibodies (proteins used by the immune system to target and kill foreign objects such as cancer cells) may have great ability to seek out, attach to, and destroy glioblastoma cells.

Start Date01 Aug 2015

Sponsor / Collaborator

Barbara Ann Karmanos Cancer Institute

[+1]

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

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

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

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7

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 ; Fadul, Camilo E ; Le, Tri ; Schiff, David ; 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 Jan 2021·OncoImmunologyQ2 · MEDICINE

Priming of pancreatic cancer cells with bispecific antibody armed activated T cells sensitizes tumors for enhanced chemoresponsiveness

Q2 · MEDICINE

ArticleOA

Author: Tomaszewski, Elyse N. ; LaBrie, Timothy M. ; Schalk, Dana L. ; Schienschang, Amy ; Ung, Johnson ; Thakur, Archana ; Lum, Lawrence G.

In this study, we investigated the ability of bispecific antibody armed activated T cells to target drug resistant pancreatic cancer cells and whether or not "priming" these resistant cancer cells with bispecific antibody armed activated T cells could enhance subsequent responsiveness to chemotherapeutic drugs. Chemotherapeutic responses for pancreatic cancer are either limited or the tumors develop resistance to chemotherapy regimens. The impetus for this study was the remarkable clinical response seen in our earlier phase I/II clinical trial: a pancreatic cancer patient with drug resistant tumors who showed progression of disease following three infusions of anti-CD3 x anti-EGFR bispecific antibody armed activated T cells (EGFR BATs) was restarted on the initial low dose of 5-fluorouracil showed complete response, suggesting that BATs infusions may have sensitized patient's tumor for chemoresponsiveness. In the current study, we tested the hypothesis that BATs can sensitize tumors for chemoresponsiveness. Gemcitabine or cisplatin-resistant MiaPaCa-2 and L3.6 cell lines were effectively targeted by EGFR BATs. Priming of drug sensitive or resistant cells with EGFR BATs followed by retargeting with lower concentrations of 50% inhibitory concentration of gemcitabine or cisplatin showed enhanced cytotoxicity. Gemcitabine or cisplatin-resistant cell lines show an increased proportion of CD44⁺/CD24⁺/EpCAM⁺ cancer stem like cells as well as an increased number of ABC transporter ABCG2 positive cells compared to the parental cell lines. These data suggest that bispecific antibody armed activated T cells can target and kill chemo-resistant tumor cells and also markedly augment subsequent chemotherapeutic responsiveness, possibly by modulating the expression of ABC transporters.

01 Jan 2021·American journal of cancer research

Aptamer-guided targeting of the intracellular long-noncoding RNA HOTAIR.

Article

Author: Chang, Ling-Chu ; Chen, Kuen-Bao ; Wang, Shao-Chun ; Wang, Yuan-Liang

Long non-coding RNAs (lncRNAs) are increasingly recognized as promising targets in cancer treatment. However, compared to targeting the ordinary protein-coding genes, suppressing non-coding RNAs expressed in cancer cells has been a more challenging task. The major hurdles lay on the requirement of a tumor-specific delivery system for the designated inhibitor to suppress the target transcripts within the cellular compartment. EGFR is a cancer driver gene which is frequently associated with the triple-negative phenotype of breast cancer. Prior studies have shown that expression of the tumor-promoting lncRNA HOTAIR (HOX antisense intergenic RNA) is positively regulated by the epithelial growth factor receptor (EGFR) in triple-negative breast cancer (TNBC), and consistently the expression of both genes is closely correlated in breast cancer. Here we show that a chimeric aptamer recognizing the epithelial growth factor receptor (EGFR) coupled with a siRNA against HOTAIR (EGFR aptamer-coupled siHOTAIR) preferentially and effectively down-regulated HOTAIR in EGFR-expressing cancer cells. Functionally, the EGFR aptamer-coupled siHOTAIR more potently inhibited the growth, migration, and invasion of EGFR-expressing TNBC cells as well as cells with reconstituted EGFR compared to cancer cells with low EGFR expression. Our results demonstrate a novel strategy of targeting cancer progression by aptamer-directed delivery of anti-lncRNA RNA interference that can be applicable to other cellular contexts and cancer types.

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

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R&D Status

10 top R&D records.

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

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Clinical Result

Indication

Phase

Evaluation

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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	(acgqxflqlr) = ddfflrdmpn ofzueqpunh (uukmzahtoh ) View more	Positive	10 Jun 2020
AACR2016	Not Applicable	Head and Neck Neoplasms	63	Cetuximab-based therapy + high ADCC + EGFR 3+ status	mbsizsejsn(tdsijreamv) = Median ADCC response at treatment start for all patients was 56.1% (range 5-99%) qckbytjxeq (ysxsyuaczp )	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)	ggumhlkeyp(uhugwhkqjg) = grade 2= 1 pt, grade 3= 1 pt nuotwbufpb (wpvjtwuyvr ) View more	-	20 May 2012

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Biosimilar

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