Delving into the Latest Updates on ALT-801 (Altor BioScience) with Synapse

Overview

Basic Info

Drug Type

Fusion protein

Synonyms

STAR-Ck

Target

IL-2R x p53

Mechanism

IL-2R antagonists(Interleukin-2 receptor antagonists), p53 inhibitors(Tumor protein p53 inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesCardiovascular Diseases+ [2]

Active Indication

Bladder CancerMultiple MyelomaAcute Myeloid Leukemia

Inactive Indication

Kidney NeoplasmsMelanomaMetastatic melanoma+ [5]

Originator Organization

Altor BioScience Corp.

Active Organization

The University of Texas MD Anderson Cancer Center

National Cancer Institute

Inactive Organization

Altor BioScience Corp.

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 19238030

This is a single-center open-label phase I clinical trial of delivering haploidentical natural killer (NK) cells matured ex vivo with ALT-801 followed by intravenous infusions of ALT-801 in patients with relapsed/refractory Acute Myeloid Leukemia (AML). The study will be conducted at M.D. Anderson Cancer Center (MDACC) and MDACC Children's Cancer Hospital in Houston, Texas.

Start Date01 Nov 2011

Sponsor / Collaborator

Altor BioScience Corp.

[+1]

NCT01029873

/ CompletedPhase 1/2

Phase Ib/II Study of ALT-801 With Cisplatin in Patients With Metastatic Melanoma

This is a Phase Ib/II, open-label, multi-center, competitive enrollment and dose-escalation study of ALT-801 combined with cisplatin. The purpose of this study is to evaluate the safety, determine the Maximum-Tolerated Dose (MTD), and characterize the pharmacokinetic profile of ALT-801 given with cisplatin in patients who are chemotherapy naïve and have metastatic melanoma that is considered surgically incurable. The anti-tumor responses of ALT-801 with cisplatin will also be assessed in this trial.

Start Date01 Feb 2010

Sponsor / Collaborator

Altor BioScience Corp.

[+1]

100 Clinical Results associated with ALT-801 (Altor BioScience)

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100 Translational Medicine associated with ALT-801 (Altor BioScience)

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100 Patents (Medical) associated with ALT-801 (Altor BioScience)

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4

Literatures (Medical) associated with ALT-801 (Altor BioScience)

15 Dec 2011·Clinical Cancer ResearchQ1 · MEDICINE

Phase I Trial of ALT-801, an Interleukin-2/T-Cell Receptor Fusion Protein Targeting p53 (aa264–272)/HLA-A*0201 Complex, in Patients with Advanced Malignancies

Q1 · MEDICINE

Article

Author: Weber, Jeffery S. ; Wong, Hing C. ; Rhode, Peter R. ; Daud, Adil I. ; Thompson, John A. ; Diez, Luz M. ; Gonzalez, Rene ; Tang, Shamay ; Pennock, Gregory K. ; Huang, Bee Y. ; Fishman, Mayer N.

AbstractPurpose: ALT-801 is a bifunctional fusion protein comprising interleukin-2 (IL-2) linked to a soluble, single-chain T-cell receptor domain that recognizes a peptide epitope (aa264–272) of the human p53 antigen displayed on cancer cells in the context of HLA-A*0201 (p53+/HLA-A*0201). We evaluated the safety, pharmacokinetics, and pharmacodynamics of ALT-801 in p53+/HLA-A*0201 patients with metastatic malignancies.Experimental Design: p53+/HLA-A*0201 patients were treated with ALT-801 on a schedule of four daily 15-minute intravenous infusions, then 10 days rest and four more daily infusions. Cohorts of patients were treated at 0.015, 0.040, and 0.080 mg/kg/dose.Results: Four, 16, and 6 patients were treated at the 0.015, 0.04, and 0.08 mg/kg cohorts, respectively. Two dose-limiting toxicities (a grade 4 transient thrombocytopenia and a myocardial infarction) in the 0.08 mg/kg cohort established the maximum tolerated dose (MTD) at 0.04 mg/kg. Patients treated at the MTD experienced toxicities similar to those associated with high-dose IL-2 but of lesser severity. The serum half-life of ALT-801 was 4 hours and ALT-801 serum recovery was as expected based on the dose administered. ALT-801 treatment induced an increase of serum IFN-γ but not TNF-α. Response assessment showed 10 subjects with stable disease at at least 11 weeks, and in one who had melanoma metastasis, there is an ongoing complete absence of identifiable disease after resection of radiographically identified lesions.Conclusion: This first-in-man study defines an ALT-801 regimen that can be administered safely and is associated with immunologic changes of potential antitumor relevance. Clin Cancer Res; 17(24); 7765–75. ©2011 AACR.

01 Oct 2006·Clinical ImmunologyQ3 · MEDICINE

Potent antitumor activity of a tumor-specific soluble TCR/IL-2 fusion protein

Q3 · MEDICINE

Article

Author: ShaMay Tang ; Jane Merrill ; Jeffrey L. Wong ; Xiaoyung Zhu ; Kai-ping Han ; Pierre-Andre Chavillaz ; Hing C. Wong ; Peter R. Rhode ; Hyung-il Lee ; Bai Liu ; Jinghai Wen ; Heather J. Belmont ; Kimberlyn F. Card ; Shari Price-Schiavi

We previously have generated a single-chain T cell receptor-cytokine fusion protein (264scTCR/IL-2) comprising interleukin-2 genetically linked to a soluble HLA-A2.1-restricted TCR recognizing a peptide of human p53 protein. In this report, we show that 264scTCR/IL-2 inhibits the growth of primary tumors derived from the A375 (p53+/HLA-A2.1+) human melanoma and exhibits significantly better antitumor activity than recombinant human IL-2 alone. Moreover, treatment with 264scTCR/IL-2 results in tumor growth retardation in mice bearing large A375 tumors and other p53+/HLA-A2.1+ human tumors but does not affect tumor outgrowth of HLA-A2.1-negative tumors. This suggests that antigen targeting plays a substantial role in the efficacy of 264scTCR/IL-2 against p53+/HLA-A2+ tumors. Further, the antitumor activity of 264scTCR/IL-2 was found to be likely mediated by NK cell activation and tumor infiltration. A biologically active chimeric version of the molecule (c264scTCR/IL-2) also exhibits favorable pharmacokinetic properties required of a clinical candidate for this novel class of potent antitumor activities and targeted anticancer immunotherapeutics.

01 Apr 2004·Cancer Immunology, ImmunotherapyQ2 · MEDICINE

A soluble single-chain T-cell receptor IL-2 fusion protein retains MHC-restricted peptide specificity and IL-2 bioactivity

Q2 · MEDICINE

Article

Author: John L. Francis ; Jon Weidanz ; Janette Builes ; Jin-an Jiao ; Ali Amirkhosravi ; Linda Sherman ; Hing C. Wong ; Javier Hernandez ; Heather Belmont ; Bai Liu ; Kimberlyn F. Card ; Elizabeth Thomson ; Shari A. Price-Schiavi ; Esperanza Nieves

Antibody-based targeted immunotherapy has shown promise as an approach to treat cancer. However, many known tumor-associated antigens are not expressed as integral membrane proteins and cannot be utilized as targets for antibody-based therapeutics. In order to expand the limited target range of antibodies, we have constructed a soluble single-chain T-cell receptor (TCR) fusion protein designated 264scTCR/IL-2. This fusion protein is comprised of a three-domain HLA-A2-restricted TCR specific for a peptide epitope of the human p53 tumor suppressor protein, which is overexpressed in a broad range of human malignancies. The 264scTCR/IL-2 fusion protein has been expressed at high levels in mammalian cells, and milligram quantities have been purified. MHC-restricted antigen-specific binding properties are maintained in the single-chain, three-domain TCR portion of the fusion protein, and the IL-2 portion retains bioactivity similar to that of free recombinant IL-2. Moreover, this fusion protein is capable of conjugating target and effector cells, remains intact in the blood and substantially increases the half life of the IL-2 portion of the molecule. Finally, the 264scTCR/IL-2 fusion protein can be used to stain tumor cells and is capable of reducing lung metastases in an experimental model of metastasis. Thus, TCR-based fusion proteins may provide a novel class of targeted immunotherapeutics for cancer.

100 Deals associated with ALT-801 (Altor BioScience)

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15386

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Kidney Neoplasms	Phase 2	US	Altor BioScience Corp.	01 Jun 2011
Mycosis Fungoides	Phase 2	US	Altor BioScience Corp.	01 Jun 2011
Ureteral Neoplasms	Phase 2	US	Altor BioScience Corp.	01 Jun 2011
Urethral Neoplasms	Phase 2	US	Altor BioScience Corp.	01 Jun 2011
Melanoma	Phase 2	US	Altor BioScience Corp.	01 Feb 2010
Metastatic melanoma	Phase 2	US	Altor BioScience Corp.	01 Feb 2010
Bladder Cancer	Phase 2	-	The University of Texas MD Anderson Cancer Center	-
Bladder Cancer	Phase 2	-	National Cancer Institute	-
Multiple Myeloma	Phase 2	-	National Cancer Institute	-
Multiple Myeloma	Phase 2	-	The University of Texas MD Anderson Cancer Center	-