Delving into the Latest Updates on INGN-225 with Synapse

Overview

Basic Info

Drug Type

Shared antigen vaccine, Therapeutic vaccine

Synonyms

Ad.p53 DC vaccine, Adenovirus-p53 transduced dendritic cell vaccine, Advexin-based-dendritic-cell-vaccine

+ [6]

Target

p53

Action

stimulants

Mechanism

P53 gene stimulants, Immunostimulants

Therapeutic Areas

NeoplasmsRespiratory DiseasesSkin and Musculoskeletal Diseases+ [1]

Active Indication-

Inactive Indication

Breast CancerBreast cancer recurrentExtensive stage Small Cell Lung Cancer+ [5]

Originator Organization

MedVax Technologies

University of Nebraska

H. Lee Moffitt Cancer Center & Research Institute, Inc.

Active Organization-

Inactive Organization

National Cancer Institute

MedVax Technologies

University of Nebraska

+ [1]

License Organization-

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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The purpose of this study is to find out what effects (good and bad) immunotherapy treatment using the p53 vaccine (Ad.p53-DC) in combination with Nivolumab and Ipilimumab has on small cell lung cancer. Immunotherapy is a cancer therapy that uses the body's immune system to fight cancer cells.
This study can be divided into three different phases: initial Induction Immunotherapy, Maintenance Immunotherapy and Retreatment.

Start Date15 Mar 2018

Sponsor / Collaborator

H. Lee Moffitt Cancer Center & Research Institute, Inc.

[+2]

NCT01302821

/ WithdrawnNot ApplicableIIT

NCI 8701: A Pilot Study Utilizing C11 Alpha Methyl Tryptophan (AMT) PET Functional Imaging in Patients With Metastatic Invasive Breast Cancer Treated With 1 Methyl D Tryptophan Plus the Ad p53 DC Vaccine

The purpose of this research project is to create images of where and how the amino acid (the building blocks of proteins)Tryptophan is processed in normal and abnormal tissue in the patient's body. Tryptophan is a normal building block of proteins in the body. Sometimes in the case of cancer and other diseases, Tryptophan is processed abnormally, and possible treatments for this abnormality are of great interest because of the potential to improve cancer care.

Start Date01 Jan 2013

Sponsor / Collaborator

H. Lee Moffitt Cancer Center & Research Institute, Inc.

[+1]

NCT01042535

/ CompletedPhase 1/2IIT

A Phase 1/2 Study of Ad.p53 DC Vaccine in Combination With 1-methyl-D-tryptophan in Metastatic Solid Tumors and Invasive Breast Cancer

This randomized phase I/II trial studies the side effects and best dose of vaccine therapy and to see how well it works when given together with 1-methyl-D-tryptophan (1-MT) in treating patients with metastatic breast cancer. Vaccines made from a person's tumor cells and white blood cells may help the body build an effective immune response to kill tumor cells.

Start Date28 Dec 2009

Sponsor / Collaborator

H. Lee Moffitt Cancer Center & Research Institute, Inc.

[+1]

100 Clinical Results associated with INGN-225

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100 Translational Medicine associated with INGN-225

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100 Patents (Medical) associated with INGN-225

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3

Literatures (Medical) associated with INGN-225

09 Feb 2018·Oncotarget

A phase-1/2 study of adenovirus-p53 transduced dendritic cell vaccine in combination with indoximod in metastatic solid tumors and invasive breast cancer

Article

Author: Soliman, Hatem ; Han, Hyo S. ; Ismail-Khan, Roohi ; Antonia, Scott ; Bui, Marilyn M. ; Sullivan, Daniel M. ; Khambati, Fatema

BACKGROUNDIndoleamine 2, 3-dioxygenase is an enzyme that causes immunosuppression in tumors. Indoximod inhibits the indoleamine 2, 3-dioxygenase pathway and enhances immunologic responses to dendritic cell (DC) vaccines preclinically. Adenovirus p53 (Ad.p53) is used to generate DC vaccines against p53. A phase-1/2 trial of indoximod with Ad.p53-DC vaccine was conducted.MATERIALS AND METHODSThe phase-1 study combined 7 indoximod dose levels with < 6 Ad.p53-DC vaccinations every 2 weeks. Primary endpoints were maximum-tolerated dose in phase 1 and objective response in phase 2. Flow cytometry measured immune responses.RESULTSThirty-nine patients were treated. In combination with Ad.p53-DC vaccine, the maximum-tolerated dose of indoximod was 1600 mg twice daily. Attributable toxicities were grade 1-2. Best response was stable disease in 4 patients. Immunologic responses were detected in 7 out of 23 evaluable patients. Median progression-free survival was 13.3 weeks (95% confidence interval, 12.97-21.85) and median overall survival was 20.71 weeks (95% confidence interval, 25.75-46.15). Nine out of 22 patients (40%) benefitted from chemotherapy after vaccination. Median overall survival in chemotherapy responders was 69.4 weeks (30.1-122.1).CONCLUSIONSIndoximod 1600 mg twice daily with Ad.p53-DC was well tolerated. There may have been a chemosensitization effect. Future trials should explore combining this treatment with chemotherapy.

01 Jun 2010·Expert Opinion on Biological TherapyQ3 · MEDICINE

INGN-225: a dendritic cell-based p53 vaccine (Ad.p53-DC) in small cell lung cancer: observed association between immune response and enhanced chemotherapy effect

Q3 · MEDICINE

Review

Author: Antonia, Scott J. ; Gabrilovich, Dmitry I. ; Chiappori, Alberto A. ; Soliman, Hatem ; Janssen, William E.

IMPORTANCE OF THE FIELDNovel approaches are needed for patients with small cell lung cancer (SCLC), as response after relapse is poor with standard therapies. p53 gene mutations often occur, resulting in tumoral protein overexpression and allowing for their recognition by p53-specific cytotoxic T cells.AREAS COVERED IN THIS REVIEWWe describe the characteristics and manufacturing of INGN-225, a p53-modified adenovirus-tranduced dendritic cell vaccine, and review available data, to understand INGN-225's role in SCLC treatment. We discuss our pre-clinical, early Phase I/II, and ongoing randomized Phase II studies.WHAT THE READER WILL GAININGN-225 was well tolerated (all toxicities TAKE HOME MESSAGEINGN-225 is safe, induces a significant immune response, and appears to sensitize SCLC to subsequent chemotherapy. Improvements in immune response induction and understanding the chemotherapy-immunotherapy synergism will determine INGN-225's future role as an anticancer therapy.

01 Dec 2008·Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases

[Anti-tumor immune response of dendritic cells transfected with wild-type p53 gene].

Article

Author: Liu, Hong-Ju ; Hu, Yu ; Li, Zhuo-Ya ; Tao, Xiao-Nan ; Xin, Jian-Bao ; Xiong, Xian-Zhi

OBJECTIVETo explore the anti-tumor immune responses of dendritic cells (DCs) loaded with intact wild-type p53 to mice challenged with tumor cells expressing p53 genes with mutations at different sites.METHODSAd-p53-DC immunization function was assessed by the expression of surface molecules and allogeneic MLR. DCs derived from bone marrow were transduced with adenovirus or a human wild-type p53 containing recombinant adenovirus (Ad-DC and Ad-p53-DC) and immunized C57BL/6 mice. Splenocytes were separated and cell cytotoxicity was measured against tumor cells expressing mutant p53 (MethA, D459 and P815) in a standard 6-h(51)Cr-release assay. Effector and target cells were incubated in the presence of anti-CD(4) or anti-CD(8) antibody. Ad-p53-DC was immunized in control Ad-DC before or after mice were challenged with either D459 tumor or with MethA sarcoma cells to observe whether immune response would provide tumor protection.RESULTSImmunization with Ad-p53-DC developed significantly higher substantial CTL responses against Ad-p53-P815, D459 and MethA cells (effectors: target cells = 50:1), (27.8 +/- 3.4)%, (23.5 +/- 2.7)%, (58.3 +/- 9.2)% than with Ad-DC (9.3 +/- 1.8)%, (4.6 +/- 1.0)%, (23.5 +/- 3.7)% (t(d) = 5.79, 3.68, 5.02, all P < 0.05). In Ad-p53-DC immunized mice, anti-CD(8) antibody blocked the cytotoxicity against Ad-p53-P815 (26.7 +/- 2.8)% or D459 (6.1 +/- 1.2)%, but not anti-CD(4) antibody [(59.8 +/- 4.6)%, (18.9 +/- 2.4)%, t(d) = 8.79 or 9.18, all P < 0.05]. Ad-p53-DC immunization provided complete tumor protection in 80% of mice challenged with D459 and in 70% of mice challenged with MethA, while none protected in Ad-DC immunization group (chi(2) = 6.72, 5.86, all P < 0.05). Treated with Ad-p53-DC after D459 inoculation subcutaneously, mice were killed due to the bulky tumor more than 2 weeks later than the mice in the Ad-DC treatment group during 7 week observation (chi(2) = 9.48, P < 0.05).CONCLUSIONDCs transfected with 100 MOI Ad-p53 induced intense CTL responses against P815, D459 and MethA. This CTL response is mediated by CD(8)(+) T cells. Treatment with Ad-p53-DC significantly developed tumor immunology and slowed the growth of established tumors.

100 Deals associated with INGN-225

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Small Cell Lung Cancer	Phase 2	United States	MedVax Technologies	26 Feb 2014
Breast cancer recurrent	Phase 2	United States	National Cancer Institute	28 Dec 2009
Invasive Mammary Carcinoma	Phase 2	United States	National Cancer Institute	28 Dec 2009
Male Breast Neoplasms	Phase 2	United States	National Cancer Institute	28 Dec 2009
Metastatic breast cancer	Phase 2	United States	National Cancer Institute	28 Dec 2009
Metastatic Solid Tumor	Phase 2	United States	National Cancer Institute	28 Dec 2009
Breast Cancer	Phase 2	United States	H. Lee Moffitt Cancer Center & Research Institute, Inc.	01 Jan 2004
Breast Cancer	Phase 2	United States	University of Nebraska	01 Jan 2004
Extensive stage Small Cell Lung Cancer	Phase 2	United States	H. Lee Moffitt Cancer Center & Research Institute, Inc.	01 Apr 2003

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03406715 (CTgov)	Phase 2	Recurrent Lung Small Cell Carcinoma	14	Ipilimumab+nivolumab+Dendritic Cell based p53 Vaccine	dtyhukyhum(mamfgzgock) = utzzmkkvjm ofrcuznzfk (oxxddrruij, tzogenfhod - rifexrssge) View more	-	30 Mar 2023
NCT00082641 (CTgov)	Phase 1/2	Breast Cancer	24	autologous dendritic cell-adenovirus p53 vaccine (Arm I)	wavdiyidsi(hkaeaggipl) = hkkvlgudpf yuipmbbomp (rkmfyqbhja, ogbpeikocm - fxujwnepag) View more	-	12 Dec 2018
NCT00082641 (CTgov)	Phase 1/2	Breast Cancer	24	autologous dendritic cell-adenovirus p53 vaccine (Arm II)	wavdiyidsi(hkaeaggipl) = gzuovhotdj yuipmbbomp (rkmfyqbhja, bdlvqwdkvc - vwtoaixvqx) View more	-	12 Dec 2018
NCT01042535 (CTgov)	Phase 1/2	Breast cancer recurrent \| Male Breast Neoplasms \| Metastatic Solid Tumor \| Metastatic breast cancer \| Invasive Mammary Carcinoma	44	Laboratory biomarker analysis+1-methyl-d-tryptophan+adenovirus-p53 transduced dendritic cell (DC) vaccine	kpaqihrlfz(ttiqfpgykf) = leqaqsqcsh rrdatefqth (bhgkphelcf, oqqepzbngj - xsctmxzrpc) View more	-	05 Mar 2015