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Neoplasms

Cytokines

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Targets

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Disease Domain	Count

Neoplasms	4

Top 5 Drug Type	Count

Cytokines	4

Top 5 Target	Count

TNFR1 x TUB	1
IFNGR1 x TNFR1	1
IAP x TNFR1	1
IL-12R x IL-2R x TNFR1	1

e14646 Background: The clinically-tested CYT-6091 nanomedicine is comprised of TNF alpha (TNF) bound to 27 nm pegylated gold nanoparticles. Preclinical research has shown that CYT-6091 disrupts solid tumor blood vessels, reduces interstitial fluid pressure and increases accumulation of follow-on chemotherapy in the tumor microenvironment. While systemic toxicity has limited treatment of cancer patients with TNF, isolated limb perfusion of patients with in-transit melanoma using 1-4 mg of TNF followed by chemotherapy has demonstrated up to 90% complete response rates with one treatment. In a single-agent, phase I clinical study in advanced-stage cancer patients, we found that multiple CYT-6091 treatments can systemically and safely deliver up to 1.2 mg of TNF per dose. Methods: Our current research was conducted to validate administering CYT-6091 prior to standard-of-care chemotherapy in a phase II clinical trial. As part of the NCI’s Experimental Therapeutics (NExT) evaluation, CYT-6091 was studied in combination with paclitaxel (PTX) in C57BL/6 murine xenografts, using three cancer cell lines: MC-38 colon carcinoma (cancer cells sensitive to TNF, but insensitive to PTX), B16/F10 melanoma (cancer cells insensitive to TNF, but sensitive to PTX), Lewis lung carcinoma (cancer cells insensitive to both TNF and PTX), where sensitivity was based on inhibiting cancer cell growth at the studied dosing amounts and frequency. CYT-6091 was administered 3-hours before PTX, and three PTX doses were administered in each model. Results: In every model, CYT-6091 + any dose of PTX was more effective in reducing or controlling tumor growth than the highest dose of PTX alone (p < 0.01). Interestingly, we also found that CYT-6091 alone demonstrated significant anti-cancer activity (p < 0.01), suggesting that additional studies may be warranted to determine optimal frequency and dose of CYT-6091 as a single agent. Conclusions: These preclinical studies demonstrate for the first time that CYT-6091 + PTX was superior to PTX (p < 0.01) or CYT-6091 alone (P < 0.05) in TNF insensitive cell lines, which represent the majority of cancers. Findings support systemically administering CYT-6091 plus standard-of-care chemotherapy in a pivotal clinical trial.

01 Sep 2018·JNCI: Journal of the National Cancer InstituteQ1 · MEDICINE

Novel Dual-Action Targeted Nanomedicine in Mice With Metastatic Thyroid Cancer and Pancreatic Neuroendocrine Tumors

Q1 · MEDICINE

Article

Author: Sanchez, Carmen ; Gaskins, Kelli ; Freedman, Esther M ; Yuan, ZiQiang ; Zhao, Jielu ; Nilubol, Naris ; Cao, Shugeng ; Libutti, Steven K ; Kingston, David G I ; Paciotti, Giulio F ; Tamarkin, Lawrence ; Kebebew, Electron

BackgroundThe advantages of nanomedicines include preferential delivery of the payload directly to tumor tissues. CYT-21625 is the novel, first-in-class gold nanomedicine designed to target tumor vasculature and cancer cells by specifically delivering recombinant human tumor necrosis factor alpha (rhTNF) and a paclitaxel prodrug.MethodsWe analyzed TNF receptor expression in publicly available gene expression profiling data and in thyroid tissue samples. Mice with metastatic FTC-133 and 8505C xenografts and the MEN1 conditional knock-out mice were treated weekly with CYT-21625 and gold nanoparticles with rhTNF only (CYT-6091); controls included mice treated with either paclitaxel or saline. In vivo luciferase activity was used to assess the effects on tumor growth. Computed tomography, magnetic resonance imaging, and 18F-Fludeoxyglucose positron emission tomography were used to study tumor selectivity in mice with insulin-secreting pancreatic neuroendocrine tumors (PNETs). All statistical tests were two-sided.ResultsAnaplastic thyroid cancer (ATC) expressed statistically significantly higher levels of TNF receptor superfamily 1A and 1B messenger RNA (n = 11) and protein (n = 6) than control samples (n = 45 and 13, respectively). Mice (n = 5-7 per group) with metastatic ATC (P < .009) and FTC-133 xenografts (P = .03 at week 3, but not statistically significant in week 4 owing to reduced sample size from death in non-CYT-21625 groups) treated with CYT-21625 had a statistically significantly lower tumor burden. Treatment with CYT-21625 resulted in loss of CD34 expression in intratumoral vasculature, decreased proliferating cell nuclear antigen, and increased cleaved caspase-3. Intratumoral vascular leakage occurred only in mice with PNET and ATC treated with CYT-6091 and CYT-21625. CYT-6091 and CYT-21625 preferentially deposited in PNETs and statistically significantly decreased serum insulin levels (n = 3 per group, P < .001). There were no toxicities observed in mice treated with CYT-21625.ConclusionsCYT-21625 is effective in mice with PNETs and metastatic human thyroid cancer with no toxicities. Thus, CYT-21625 should be studied in patients with advanced PNETs and thyroid cancer.

01 Jun 2017·Therapeutic Delivery

Exposing the Tumor microenvironment: How Gold Nanoparticles Enhance and Refine Drug Delivery

Review

Author: Tamarkin, Lawrence ; Kingston, David G I

Exposing the tumor microenvironment: how gold nanoparticles enhance and refine drug delivery.

100 Deals associated with CytImmune Sciences, Inc.

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100 Translational Medicine associated with CytImmune Sciences, Inc.

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Pipeline

Pipeline Snapshot as of 26 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Preclinical

4

7

Other

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

CYT-IL12 3 IL2 TNFa(CytImmune Sciences) ( IL-12R x IL-2R x TNFR1 )	Solid tumor More	Preclinical
CYT-IFNγ 2 TNFa(CytImmune Sciences) ( IFNGR1 x TNFR1 )	Solid tumor More	Preclinical
CYT-PTX 2 TNFa(CytImmune Sciences) ( TNFR1 x TUB )	Solid tumor More	Preclinical
CYT-IAPi 2 TNFα(CytImmune Sciences) ( IAP x TNFR1 )	Solid tumor More	Preclinical
CYT-CDR2 ( PDL1 x TNF-α )	Neoplasms More	Discontinued