Delving into the Latest Updates on VSSP (Center of Molecular Immunology) with Synapse

Overview

Basic Info

Drug Type

Protein drugs

Synonyms

VSSP

Target

GM3

Mechanism

GM3 inhibitors(G(M3) Ganglioside inhibitors)

Therapeutic Areas

Immune System DiseasesInfectious DiseasesUrogenital Diseases

Active Indication

Acquired Immunodeficiency Syndrome

Inactive Indication

Kidney NeoplasmsVaccination

Originator Organization

Center For Molecular Immunology

Active Organization

Center For Molecular Immunology

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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AbstractMacrophages represent the most abundant immune component of the tumor microenvironment and often exhibit protumorigenic (M2-like) phenotypes that contribute to disease progression. Despite their generally accepted protumorigenic role, macrophages can also display tumoricidal (or M1-like) behavior, revealing that macrophages can be functionally reprogrammed, depending on the cues received within the tumor microenvironment. Moreover, such plasticity may be achieved by pharmacologic or biologic interventions. To that end, we previously demonstrated that a novel immunomodulator termed the “very small size particle” (VSSP) facilitates maturation of dendritic cells and differentiation of myeloid-derived suppressor cells to APCs with reduced suppressive activity in cancer models. VSSP was further shown to act in the bone marrow to drive the differentiation of progenitors toward monocytes, macrophages, and dendritic cells during emergency myelopoiesis. However, the underlying mechanisms for VSSP-driven alterations in myeloid differentiation and function remained unclear. In this study, in mouse models, we focused on macrophages and tested the hypothesis that VSSP drives macrophages toward M1-like functional states via IRF8- and PU.1-dependent mechanisms. We further hypothesized that such VSSP-mediated actions would be accompanied by enhanced antitumor responses. Overall, we showed that (1) VSSP drives naive or M2-derived macrophages to M1-like states, (2) the M1-like state induced by VSSP occurs via IRF8- and PU.1-dependent mechanisms, and (3) single-agent VSSP induces an antitumor response that is accompanied by alterations in the intratumoral myeloid compartment. These results provide a deeper mechanistic underpinning of VSSP and strengthen its use to drive M1-like responses in host defense, including cancer.

01 Aug 2023·Journal of vascular and interventional radiology : JVIR

Dural Venous Sinus Stent Placement Reduces Dosage Requirements for Carbonic Anhydrase Inhibitors in Patients with Idiopathic Intracranial Hypertension.

Article

Author: Martin, Jesse ; Sanborn, Matthew R

This retrospective single-center study evaluated the change in required dosage of acetazolamide and topiramate before and after dural venous sinus stent placement (VSSP) for idiopathic intracranial hypertension (IIH). Adults diagnosed with IIH who failed optimized medical management and were treated with VSSP were included. This study comprised 55 patients who underwent VSSP for the diagnosis of IIH. The median preprocedural dosage of acetazolamide and topiramate was 1,000 mg (range, 500-4,000 mg) and 100 mg (range, 0-200 mg), respectively, among patients able to tolerate the medications. The median postprocedural dosage of acetazolamide and topiramate was 375 mg (range, 0-4,000 mg), with a mean reduction of 52.9% (P = .001), and 0 mg (range, 0-200 mg), with a mean reduction of 45.9% (P = .005), respectively. Dural VSSP significantly reduced dosage requirements for acetazolamide and/or topiramate, potentially reducing the morbidity secondary to medication side effects.

13 Apr 2023·Cell communication and signaling : CCS

VSSP-activated macrophages mediate senescence and tumor inhibition in a preclinical model of advanced prostate cancer.

Article

Author: Bancaro, Nicoló ; Troiani, Martina ; Mosole, Simone ; Pellegrini, Laura ; Attanasio, Giuseppe ; Mesa, Circe ; Lai, Ping ; Alimonti, Andrea ; Pasquini, Emiliano ; Alvarez-Arzola, Rydell ; Colucci, Manuel

Androgen deprivation therapy (ADT) is a standard therapy for prostate cancer (PCa). Though disseminated disease is initially sensitive to ADT, an important fraction of the patients progresses to castration-resistant prostate cancer (CRPC). For this reason, the identification of novel effective therapies for treating CRPC is needed. Immunotherapeutic strategies focused on macrophages as antitumor effectors, directly enhancing their tumoricidal potential at the tumor microenvironment or their adoptive transfer after ex vivo activation, have arisen as promising therapies in several cancer types. Despite several approaches centered on the activation of tumor-associated macrophages (TAMs) in PCa are under investigation, to date there is no evidence of clinical benefit in patients. In addition, the evidence of the effectiveness of macrophage adoptive transfer on PCa is poor. Here we find that VSSP, an immunomodulator of the myeloid system, decreases TAMs and inhibits prostatic tumor growth when administered to castrated Pten-deficient prostate tumor-bearing mice. In mice bearing castration-resistant Pten^pc-/-; Trp53^pc-/- tumors, VSSP administration showed no effect. Nevertheless, adoptive transfer of macrophages activated ex vivo with VSSP inhibited Pten^pc-/-; Trp53^pc-/- tumor growth through reduction of angiogenesis and tumor cell proliferation and induction of senescence. Taken together, our results highlight the rationale of exploiting macrophage functional programming as a promising strategy for CRPC therapy, with particular emphasis on ex vivo-activated proinflammatory macrophage adoptive transfer. Video abstract.

100 Deals associated with VSSP (Center of Molecular Immunology)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acquired Immunodeficiency Syndrome	Phase 1	-	Center For Molecular Immunology	01 Jan 2006
Kidney Neoplasms	Preclinical	CU	Center For Molecular Immunology	22 Feb 2013
HIV Infections	Preclinical	CU	Center For Molecular Immunology	28 Apr 2011
Vaccination	Preclinical	CU	Center For Molecular Immunology	28 Apr 2011

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


IAS2011	Not Applicable	HIV Infections	22	VSSP (Group A)	enzqfbwrfl(bjtjwkxafw) = ykrdcvhtei egrmlpdxrn (tlfetisdqi ) View more	-	01 Jan 2011
				VSSP (Group B)	enzqfbwrfl(bjtjwkxafw) = haohsubuhu egrmlpdxrn (tlfetisdqi ) View more