Delving into the Latest Updates on HA-pHLIP with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

Target

hemagglutinin

Mechanism

hemagglutinin inhibitors(Influenza virus hemagglutinin glycoproteins inhibitors)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal Diseases

Active Indication

Melanoma

Inactive Indication-

Originator Organization

University of Rhode Island

Active Organization

University of Rhode Island

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

CAR-T cells and monoclonal antibodies (mAbs) are immunotherapeutics that have shown efficacies against certain malignancies. However, their broad application is hindered by the scarcity of tumor-associated antigens on tumor cell surfaces. Previous investigations unveiled the unique capacity of pH-low insertion peptide (pHLIP) to anchor to plasma membranes under acidic conditions. Considering that an acidic tumor microenvironment is a hallmark of solid tumors, we engineered a novel peptide, Myc-pHLIP, by tethering a surrogate epitope tag, the c-Myc-tag, to pHLIP. We evaluated the efficiency of Myc-pHLIP in inserting the artificial c-Myc-tag onto the plasma membrane of malignant cells and determined if this engraftment could convert it into a therapeutic target for CAR-T cells or mAbs. Our in vitro experiments demonstrated that incubating Myc-pHLIP with tumor cells in acidic media triggered significant killing by either Myc-targeted CAR-T cells (Myc-CAR-T), or by an anti-Myc mAb in the presence of NK cells. In vivo studies demonstrated substantial antitumor effects with sequential administration of Myc-pHLIP followed by either Myc-CAR-T or Myc-mAb. These findings establish that Myc-pHLIP has the potential to act as a universal surrogate tumor antigen capable of directing CAR-T cells or mAbs to treat any solid tumors by concurrently targeting both malignant and stromal cells.

100 Deals associated with HA-pHLIP

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