Delving into the Latest Updates on 131I-CC49-SCA with Synapse

Overview

Basic Info

Drug Type

Single-chain FV antibody fragment

Synonyms

212 SCA, CC 49, CC-49-single chain antibodies (Enzon)

+ [3]

Target

TAG-72

Mechanism

TAG-72 antagonists(Tumor-associated glycoprotein 72 antagonists)

Therapeutic Areas

NeoplasmsDigestive System Disorders

Active Indication

Colonic Cancer

Inactive Indication

Cardiovascular Diseases

Originator Organization

SCA Ventures, Inc.

Active Organization

Toronto General HospitalOntario Cancer Institute

Inactive Organization

National Cancer InstituteSCA Ventures, Inc.

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

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Gene Sequence

Sequence Code 468529L

Source: *****

Sequence Code 468533H

Source: *****

Tumor-associated glycoprotein 72 (TAG-72) is a mucin that is overexpressed heterogeneously on the surface of cancer cells, and is a potential target for immunotherapies for various cancer types. As a tumor marker, TAG-72 is measured with the cancer antigen (CA) 72-4 immunoassay. The murine monoclonal antibody (mAb) CC49 is a second-generation IgG that targets an antigen on TAG-72; however, CC49 has an unfavorable propensity to aggregate, which results in antibody impurity, instability, and low solubility and thus low potency and efficacy for therapeutic and diagnostic applications. Sequence analysis of CC49 revealed aggregation-prone motifs in the variable domain of the light chain. Using antibody engineering approaches, we developed three aggregation-resistant CC49 mIgG2a mutants (CC49M1, CC49M2, and CC49M3). The engineered CC49 mIgG2a mutants retained compatible binding performance with a significantly higher thermal stability. The CC49 mIgG2a mutants also demonstrated an almost 15-fold improvement in solubility, with 97% purity vs 70% purity of the parent molecule at 0.3 mg/mL. The enhanced stability and improved solubility of engineered CC49 could have significant advantages for diagnostic and therapeutic applications.

01 Aug 2020·The Journal of surgical researchQ4 · MEDICINE

Humanized Anti–Tumor-Associated Glycoprotein–72 for Submillimeter Near-Infrared Detection of Colon Cancer in Metastatic Mouse Models

Q4 · MEDICINE

Article

Author: Michael Bouvet ; Paul J. Yazaki ; Robert M. Hoffman ; Justin Molnar ; Siamak Amirfakhri ; Filemoni Filemoni ; Hannah M. Hollandsworth

BACKGROUND:

Tumor-associated glycoprotein (TAG)-72 is a pancarcinoma antigen that is overexpressed in greater than 80% of colorectal adenocarcinomas. CC49 is a TAG-72-specific antibody. The aim of the present study was to demonstrate selective imaging of colon tumors and metastases with the humanized TAG-72 antibody (anti-huCC49) conjugated to a near-infrared fluorophore in orthotopic mouse models.

METHODS:

Anti-huCC49 was conjugated to near-infrared dye IR800CW. Mouse imaging was performed with the Pearl Trilogy Small Animal and FLARE Imaging Systems. Subcutaneous mouse models of colon cancer cell line LS174T were used to determine the optimal dose of administration and timing of imaging. Orthotopic mouse models of LS174T were established by surgical orthotopic implantation of LS174T tumors onto the serosa of the cecum. Peritoneal carcinomatosis models were established by injection of LS174T cells into the peritoneum of nude mice. Mice were administered anti-huCC49-IR800 via tail vein injection. Mice were euthanized 72 h later and imaged after laparotomy.

RESULTS:

Subcutaneous LS174T xenografts demonstrated optimal tumor detection 72 h after administration with 50 μg anti-huCC49-IR800CW. Tumors were visualized with fluorescence imaging with a mean tumor-to-liver ratio of 7.39 (standard deviation: 2.76). In the orthotopic model, metastases smaller than 1 mm were fluorescently visualized that were invisible with bright light.

CONCLUSIONS:

Anti-huCC49-IR800CW provides sensitive and specific imaging of colon cancer and metastases at a submillimeter resolution in metastatic nude mice models. This provides a promising near-infrared probe for the imaging of colon cancer and metastases for preoperative diagnosis and fluorescence-guided surgery.

01 Jul 2020·Cancer medicineQ3 · MEDICINE

Improved targeting of an anti‐TAG‐72 antibody drug conjugate for the treatment of ovarian cancer

Q3 · MEDICINE

ArticleOA

Author: Poku, Erasmus ; Li, Lin ; Minnix, Megan ; Shively, John E. ; Colcher, David ; Yazaki, Paul ; Chea, Junie

Abstract:

Introduction:

Ovarian cancer has only a 17% 5‐year survival rate in patients diagnosed with late stage disease. Tumor‐associated glycoprotein‐72 (TAG72), expressed in 88% of all stages of ovarian cancer, is an excellent candidate for antibody‐targeted therapy, as it is not expressed in normal human adult tissues, except in the secretory endometrium.

Methods:

Using the clinically relevant anti‐TAG72 murine monoclonal antibody CC49, we evaluated antibody drug conjugates (ADCs) incorporating the highly potent, synthetic antimitotic agent monomethylauristatin E (MMAE). MMAE was conjugated to CC49 via reduced disulfides in the hinge region, using three different types of linker chemistry, vinylsulfone (VS‐MMAE), bromoacetamido (Br‐MMAE), and maleimido (mal‐MMAE).

Results:

The drug antibody ratios (DARs) of the three ADCs were 2.3 for VS‐MMAE, 10 for Br‐MMAE, and 9.5 for mal‐MMAE. All three ADCs exhibited excellent tumor to blood ratios on PET imaging, but the absolute uptake of CC49‐mal‐MMAE (3.3%ID/g) was low compared to CC49‐Br‐MMAE (6.43%ID/g), at 142 hours. Blood clearance at 43 hours was 38% for intact CC49, about 24% for both CC49‐VS‐MMAE and CC49‐Br‐MMAE, and 7% for CC49‐mal‐MMAE. CC49‐VS‐MMAE was not further studied due to its low DAR, while CC49‐mal‐MMAE was ineffective in the OVCAR3 xenograft likely due to its rapid blood clearance. In contrast, CC49‐Br‐MMAE treated mice exhibited an average of a 15.6 day tumor growth delay and a 40% increase in survival vs controls with four doses of 7.5 or 15 mg/kg of CC49‐Br‐MMAE.

Conclusion:

We conclude that CC49‐Br‐MMAE with a high DAR and stable linker performs well in a difficult to treat solid tumor model.

100 Deals associated with 131I-CC49-SCA

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External Link

KEGG	Wiki	ATC	Drug Bank
-	131I-CC49-SCA	-	DB15470

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Cardiovascular Diseases	Phase 1	US	SCA Ventures, Inc.	-
Cardiovascular Diseases	Phase 1	US	National Cancer Institute	-
Neoplasms	Phase 1	US	National Cancer Institute	-
Neoplasms	Phase 1	US	SCA Ventures, Inc.	-
Colonic Cancer	Preclinical	CA	Ontario Cancer Institute	01 Apr 2004
Colonic Cancer	Preclinical	CA	Toronto General Hospital	01 Apr 2004