Delving into the Latest Updates on Disomotide with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

Disomotide (USAN/INN)

+ [4]

Target

gp100

Action

inhibitors

Mechanism

gp100 inhibitors(Melanocyte protein PMEL inhibitors)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal Diseases

Active Indication

Melanoma

Inactive Indication-

Originator Organization

Bristol Myers Squibb Co.

Active Organization

Bristol Myers Squibb Co.

Inactive Organization-

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC47H74N10O14S

InChIKeyBDQMCYCLZBSYJZ-BBXCZNCNSA-N

CAS Registry181477-43-0

Sequence Code 101057

Source: *****

RATIONALE: Vaccines made from a patient's dendritic cells may make the body build an immune response to kill tumor cells. It is not yet known whether combining vaccine therapy with either gp100 antigen or the patient's tumor cells will cause a stronger immune response and kill more tumor cells.
PURPOSE: This randomized phase II trial is studying vaccine therapy and gp100 antigen to see how well they work compared to vaccine therapy and patient's tumor cells in treating patients with stage III or stage IV melanoma.

Start Date01 Mar 2004

Sponsor / Collaborator

Dana-Farber Cancer Institute, Inc.

[+1]

NCT00019214

/ CompletedPhase 1/2IIT

Phase I/II Study in Patients With Metastatic Melanoma of Immunization With Dendritic Cells Presenting Epitopes Derived From The Melanoma Associated Antigens MART-1 and gp 100

RATIONALE: Vaccines made from white blood cells treated with antigens may make the body build an immune response to kill melanoma cells. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. Combining vaccine therapy with interleukin-2 may kill more melanoma cells.
PURPOSE: This phase I/II trial is studying the side effects and how well giving vaccine therapy and interleukin-2 works compared to vaccine therapy alone in treating patients with metastatic melanoma that has not responded to previous therapy.

Start Date01 Apr 1997

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with Disomotide

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100 Translational Medicine associated with Disomotide

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100 Patents (Medical) associated with Disomotide

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121

Literatures (Medical) associated with Disomotide

05 Jun 2024·Journal of the American Chemical Society

Proteomimetic Polymers Trigger Potent Antigen-Specific T Cell Responses to Limit Tumor Growth

Article

Author: Evangelopoulos, Michael ; Battistella, Claudia ; Mirkin, Chad A ; Gattis, Brayley ; Wang, Max M ; Choi, Mi-Ran ; Zhang, Bin ; Olvera de la Cruz, Monica ; Qiao, Baofu ; Gianneschi, Nathan C

Elicitation of effective antitumor immunity following cancer vaccination requires the selective activation of distinct effector cell populations and pathways. Here we report a therapeutic approach for generating potent T cell responses using a modular vaccination platform technology capable of inducing directed immune activation, termed the Protein-like Polymer (PLP). PLPs demonstrate increased proteolytic resistance, high uptake by antigen-presenting cells (APCs), and enhanced payload-specific T cell responses. Key design parameters, namely payload linkage chemistry, degree of polymerization, and side chain composition, were varied to optimize vaccine formulations. Linking antigens to the polymer backbone using an intracellularly cleaved disulfide bond copolymerized with a diluent amount of oligo(ethylene glycol) (OEG) resulted in the highest payload-specific potentiation of antigen immunogenicity, enhancing dendritic cell (DC) activation and antigen-specific T cell responses. Vaccination with PLPs carrying either gp100, E7, or adpgk peptides significantly increased the survival of mice inoculated with B16F10, TC-1, or MC38 tumors, respectively, without the need for adjuvants. B16F10-bearing mice immunized with gp100-carrying PLPs showed increased antitumor CD8⁺ T cell immunity, suppressed tumor growth, and treatment synergy when paired with two distinct stimulator of interferon gene (STING) agonists. In a human papillomavirus-associated TC-1 model, combination therapy with PLP and 2'3'-cGAMP resulted in 40% of mice completely eliminating implanted tumors while also displaying curative protection from rechallenge, consistent with conferment of lasting immunological memory. Finally, PLPs can be stored long-term in a lyophilized state and are highly tunable, underscoring the unique properties of the platform for use as generalizable cancer vaccines.

01 Jun 2024·Journal for ImmunoTherapy of Cancer

Long-term survival follow-up for tebentafusp in previously treated metastatic uveal melanoma

Article

Author: Holland, Chris ; Johnson, Douglas B ; Sacco, Joseph J ; Carvajal, Richard D ; Piulats, Josep M ; Espinosa, Enrique ; Luke, Jason J ; Nathan, Paul ; Hamid, Omid ; Shoushtari, Alexander N ; Butler, Marcus O ; Leyvraz, Serge ; Rioth, Matthew ; Sato, Takami ; Collins, Laura ; Ikeguchi, Alexandra ; Hassel, Jessica C ; Hernandez-Aya, Leonel

BackgroundTebentafusp, a bispecific (gp100×CD3) ImmTAC, significantly improved overall survival (OS) outcomes for HLA-A*02:01+ adult patients with untreated metastatic uveal melanoma (mUM) and showed promising survival in previously treated mUM with 1-year OS of 62% in the primary analysis of study IMCgp100-102. Here we report long-term outcomes from this phase 1/2 study in pretreated mUM.Patients and methodsPatients with previously treated mUM received tebentafusp weekly intravenous at 20 µg dose 1, 30 µg dose 2 and either 54, 64, 68, or 73 µg (phase 1) or 68 µg (phase 2) dose 3+. The primary objective was overall response rate. Secondary objectives included OS and safety. OS was estimated by Kaplan-Meier methods. Association between OS and baseline covariates, on-treatment Response Evaluation Criteria in Solid Tumors (RECIST) response, baseline tumor biopsy and circulating-tumor DNA (ctDNA) changes were assessed.Results146 patients were treated with tebentafusp: 19 in phase 1 and 127 in phase 2. With a median follow-up duration of 48.5 months, the median OS was 17.4 months (95% CI, 13.1 to 22.8), and the 1-year, 2-year, 3-year and 4-year OS rates were 62%, 40%, 23% and 14%, respectively. Improved survival was associated with lower ctDNA baseline levels and greater ctDNA reductions by week 9 on-treatment, with 100% 1-year, 73% 2-year and 45% 3-year OS rates for patients with ctDNA clearance. Baseline gp100 expression was not associated with survival, despite more RECIST responses among patients with higher expression. No new safety signals were reported with long-term dosing.ConclusionsThis study represents the longest follow-up of a Tcell receptor bispecific to date and confirms the durable survival benefits achieved with tebentafusp in previously treated mUM with good tolerability long-term. A role for ctDNA reduction as an early indicator of clinical benefit was again suggested for patients treated with tebentafusp.

01 May 2023·Amino acids

Glycine protects against doxorubicin-induced heart toxicity in mice.

Article

Author: Saad, Entsar A. ; El-Ablack, Fawzia Z. ; Shosha, Mayada I.

Doxorubicin (DOXO) is a well-known cancer chemotherapeutic. However, its toxic effect on the heart limits its clinical application. This study aimed to assess the effectiveness of glycine administration to counteract the DOXO-induction of cardiomyopathy in mice. Fifty male albino mice were divided into five groups (n = 10/group) as follows: control, DOXO, Gp100, Gp150, and Gp200. Histopathological examination of the heart, and biochemical examinations for heart function (creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST)), inflammation (tumor necrosis factor-alpha (TNF-α) and interleukin 10 (IL-10)), oxidative stress (malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase, nitric oxide (NO), and uric acid), kidney function (urea and creatinine), and minerals (calcium, phosphorus, sodium, and potassium) were carried out. Cardiomyopathy induced by DOXO treatment (15 mg/kg total dose) was ascertained via pathological alterations seen in heart tissue and verified biochemically via increases (P < 0.001) in CPK, LDH, AST, TNF-α, IL-10, MDA, NO, Na, and K levels along with decreases (P < 0.001) in GSH, SOD, catalase, and uric acid. Glycine co-treatment, using doses of 100, 150, and 200 mg/kg, in a dose-dependent manner, displayed ameliorated heart architecture, significantly (P < 0.001) improved biochemical heart function tests, reduced oxidative stress and inflammation, and controlled mineral levels. The positive actions of glycine in DOXO-induced cardiotoxicity amelioration via modulating oxidative stress, inflammation, and immunity are confirmed. Glycine antioxidative properties may be behind its positive outcomes. Finally, we present glycine as a worthy possible option against DOXO-induced heart damage after more validation.

100 Deals associated with Disomotide

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External Link

KEGG	Wiki	ATC	Drug Bank
D06581	-	-	-

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Melanoma	Phase 3	-	Bristol Myers Squibb Co.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2010	Not Applicable	Metastatic melanoma	179	Ipilimumab with gp100 peptide vaccines	(bjhfyzmltx) = gnqkiinxkt ereemejywd (rxklsbvaqv ) View more	Positive	20 May 2010
				Ipilimumab with high-dose interleukin-2 (IL-2)	(bjhfyzmltx) = cqlkaglzdm ereemejywd (rxklsbvaqv ) View more
ASCO2010	Phase 3	Unresectable Melanoma	643	Ipilimumab	(xytpsghshb) = drvjpadevj lnonbxudwe (zllmrmzmbm )	-	20 May 2010
				Ipilimumab + gp100 vaccine	(xytpsghshb) = hhuiiaxzfv lnonbxudwe (zllmrmzmbm )
AACR2009	Phase 1	Melanoma	19	Xenogeneic gp100 DNA	(aauefkcuam) = qxrtdrayao pmsncdvezi (fchhwxpgou ) View more	-	01 May 2009
ASCO2006	Phase 1	Melanoma	-	gp100 (Group I)	xyvjlxdoly(oxivegujgy) = qhkygleqpt omogbazkbj (efuwjtarnn ) View more	-	20 Jun 2006
				gp100 (Group II)	nammbovurq(wnkmncqvdk) = xuaieubsyh xzwefeadab (viqedruarj )

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Biosimilar

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