Delving into the Latest Updates on ISF-35 with Synapse

Overview

Basic Info

Drug Type

Recombinant protein

Synonyms

Ad-ISF35 transduced CLL B-cells, Immune Stimulatory Factor 35

+ [5]

Target

CD40

Action

agonists

Mechanism

CD40 agonists(Tumor necrosis factor receptor superfamily member 5 agonists)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [1]

Active Indication-

Inactive Indication

Chronic lymphocytic leukaemia refractoryChronic Lymphocytic LeukemiaDiffuse Large B-Cell Lymphoma+ [5]

Originator Organization

Memgen, Inc.

Active Organization-

Inactive Organization

Memgen, Inc.UCSD Moores Cancer Center

License Organization-

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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The goal of this clinical research study is to find the highest tolerated dose of rAd.CD40L (also called ISF35) when given with pembrolizumab to patients with melanoma. Researchers also want to learn if the highest tolerated dose of ISF35 and pembrolizumab can help to control the disease.
The safety of this drug combination will be also be studied.

Start Date01 Mar 2018

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

[+1]

NCT00942409

/ TerminatedPhase 2IIT

A Phase II Study of Repeat Intranodal Injections of Adenovirus-CD154 (Ad-ISF35) in Patients With Non-Hodgkin's Lymphoma (Follicular, Diffuse Large Cell, Mantle Cell and Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia)

This is a Phase II, open label, fixed dose, repeat injection, single institution study. Eligible subjects will receive up to six doses of Ad-ISF35 injected directly into a selected lymph node under ultrasound guidance. The primary goal is to determine and monitor clinical and biological responses in patients treated with repeat intranodal injections of Ad-ISF35.

Start Date01 Jun 2009

Sponsor / Collaborator

University of California San Diego

[+1]

NCT00849524

/ TerminatedPhase 2IIT

A Phase II Study of Repeat Intranodal Injections of Adenovirus-CD 154 (Ad-ISF35) in Patients With Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma

This is a Phase II, open label, fixed dose, repeat injection, single institution study. Eligible subjects will receive up to six doses of Ad-ISF35 injected directly into a selected lymph node under ultrasound guidance. The primary goal is to determine and monitor clinical and biological responses in patients treated with repeat intranodal injections of Ad-ISF35.

Start Date01 Jan 2009

Sponsor / Collaborator

University of California San Diego

[+1]

100 Clinical Results associated with ISF-35

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100 Translational Medicine associated with ISF-35

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100 Patents (Medical) associated with ISF-35

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9

Literatures (Medical) associated with ISF-35

01 Jan 2015·Human Gene TherapyQ2 · MEDICINE

Intratumoral Injection of Ad-ISF35 (Chimeric CD154) Breaks Tolerance and Induces Lymphoma Tumor Regression

Q2 · MEDICINE

Article

Author: Kipps, Thomas J. ; Urquiza, Mauricio ; Castro, Januario E. ; Aguillon, Robier ; Melo-Cardenas, Johanna

Ad-ISF35, an adenovirus vector encoding a membrane-bound engineered CD154 chimeric protein (ISF35), induces complete A20 lymphoma tumor regression in mice after intratumoral direct injection (IDI). Ad-ISF35 induced durable local and systemic antitumor responses associated with a rapid tumor infiltration of macrophages and neutrophils as well as increased levels of proinflammatory cytokines in the tumor microenvironment. Ad-ISF35 IDI transduced preferentially fibroblasts and macrophages present in the tumor microenvironment, and ISF35 protein expression was observed in only 0.25% of cells present in the tumor. Moreover, Ad-ISF35 IDI induced upregulation of CD40 in tumor and immune regulatory cells, including those that did not express ISF35, suggesting the presence of a strong bystander effect. These responses resulted in the generation of IFN-γ-secreting cytotoxic lymphocytes and the production of specific cytotoxic antibodies against lymphoma cells. Overall, cellular immune therapy based on ISF35 induced phenotypic changes in the tumor cells and tumor microenvironment that were associated with a break in tumor immune tolerance and a curative antitumor effect in this lymphoma mouse model. Our data highlight the potential activity that modulation of costimulatory signaling has in cancer therapy.

01 Mar 2014·Cancer Immunology, ImmunotherapyQ2 · MEDICINE

Enhanced therapeutic anti-tumor immunity induced by co-administration of 5-fluorouracil and adenovirus expressing CD40 ligand

Q2 · MEDICINE

Article

Author: Dimitra Vyrla ; Aristides G. Eliopoulos ; Emma Svensson ; Angelica Si Loskog ; Lina Liljenfeldt ; Katerina Gkirtzimanaki

Bystander immune activation by chemotherapy has recently gained extensive interest and provided support for the clinical use of chemotherapeutic agents in combination with immune enhancers. The CD40 ligand (CD40L; CD154) is a potent regulator of the anti-tumor immune response and recombinant adenovirus (RAd)-mediated CD40L gene therapy has been effective in various cancer models and in man. In this study we have assessed the combined effect of local RAd-CD40L and 5-fluorouracil (5-FU) administration on a syngeneic MB49 mouse bladder tumor model. Whereas MB49 cells implanted into immunocompetent mice responded poorly to RAd-CD40L or 5-FU alone, administration of both agents dramatically decreased tumor growth, increased survival of the mice and induced systemic MB49-specific immunity. This combination treatment was ineffective in athymic nude mice, highlighting an important role for T cell mediated anti-tumor immunity for full efficacy. 5-FU up-regulated the expression of Fas and immunogenic cell death markers in MB49 cells and cytotoxic T lymphocytes from mice receiving RAd-CD40L immunotherapy efficiently lysed 5-FU treated MB49 cells in a Fas ligand-dependent manner. Furthermore, local RAd-CD40L and 5-FU administration induced a shift of myeloid-derived suppressor cell phenotype into a less suppressive population. Collectively, these data suggest that RAd-CD40L gene therapy is a promising adjuvant treatment to 5-FU for the management of bladder cancer.

15 Jun 2012·Cancer ResearchQ1 · MEDICINE

Gene Immunotherapy of Chronic Lymphocytic Leukemia: A Phase I Study of Intranodally Injected Adenovirus Expressing a Chimeric CD154 Molecule

Q1 · MEDICINE

Article

Author: Urquiza, Mauricio ; Castro, Januario E. ; Barajas-Gamboa, Juan S. ; Pakbaz, Ramin S. ; Melo-Cardenas, Johanna ; Kipps, Thomas J.

AbstractNew therapies for chronic lymphocytic leukemia (CLL) are needed, particularly those that can eradicate residual disease and elicit anti-CLL immune responses. CD40 ligation on CLL cells, which can be achieved using adenovirus encoding chimeric CD154 (Ad-ISF35), enhances their ability to function as antigen-presenting cells and increases their sensitivity to clearance by immune-effector mechanisms. In this study, we report the results of a first-in-man phase I trial of intranodal direct injection (IDI) of Ad-ISF35 in patients with CLL to evaluate toxicity, safety, and tolerability. Fifteen patients received a single IDI of 1 × 1010 to 33 × 1010 Ad-ISF35 viral particles (vp), with a defined maximum tolerated dose as 1 × 1011 vp. Although the most common adverse events were transient grade 1 to 2 pain at the injection site and flu-like symptoms following IDI, some patients receiving the highest dose had transient, asymptomatic grade 3 to 4 hypophosphatemia, neutropenia, or transaminitis. Increased expression of death receptor, immune costimulatory molecules, and Ad-ISF35 vector DNA was detected in circulating CLL cells. Notably, we also observed preliminary clinical responses, including reductions in leukemia cell counts, lymphadenopathy, and splenomegaly. Six patients did not require additional therapy for more than 6 months, and three achieved a partial remission. In conclusion, Ad-ISF35 IDI was safely delivered in patients with CLLs and induced systemic biologic and clinical responses. These results provide the rationale for phase II studies in CLLs, lymphomas, and CD40-expressing solid tumors. Cancer Res; 72(12); 2937–48. ©2012 AACR.

100 Deals associated with ISF-35

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Refractory Melanoma	Phase 2	-	Memgen, Inc.	01 Mar 2018
Diffuse Large B-Cell Lymphoma	Phase 2	United States	Memgen, Inc.	01 Jun 2009
Follicular Lymphoma	Phase 2	United States	Memgen, Inc.	01 Jun 2009
Mantle-Cell Lymphoma	Phase 2	United States	Memgen, Inc.	01 Jun 2009
Chronic Lymphocytic Leukemia	Phase 2	United States	Memgen, Inc.	01 Jan 2009
Small Lymphocytic Lymphoma	Phase 2	United States	Memgen, Inc.	01 Jan 2009
Chronic lymphocytic leukaemia refractory	Phase 2	United States	Memgen, Inc.	01 Sep 2008
Non-Hodgkin Lymphoma	Phase 2	United States	UCSD Moores Cancer Center	01 May 2007

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00942409 (CTgov)	Phase 2	Mantle-Cell Lymphoma \| Follicular Lymphoma \| Chronic Lymphocytic Leukemia \| Diffuse Large B-Cell Lymphoma \| Small Lymphocytic Lymphoma	5	ISF35	znyutsjqai(sehatopjzo) = coztaclikb mbnjxscufe (aqkctkmmak, wdclvwiamx - gerrhsghgy) View more	-	20 Nov 2015
NCT00849524 (CTgov)	Phase 2	Chronic Lymphocytic Leukemia \| Small Lymphocytic Lymphoma	6	ISF35	uqzuqcdvtq(izxttdmbbr) = pqwoyflwur hhuvukaxfw (bjfkkyyqwe, nmhbmycamw - oausnzummi) View more	-	20 Nov 2015
AACR2009	Phase 1	Chronic Lymphocytic Leukemia	15	Ad-ISF35 viral particles	(vquzarquxt) = asymptomatic and transient Grade 3 or 4 iazekjoqey (tipiaocton ) View more	-	01 May 2009

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Biosimilar

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