Drug intelligence / Profile preview

TILT-123 + pembrolizumab + pegylated liposomal doxorubicin

Development stage
Phase 2
Lead developer
TILT Biotherapeutics
Modality
Oncolytic Viruses → Oncolytic Therapeutics, Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules, Nanoparticles → Drug Delivery Systems
Administration
Intravenous, Intraperitoneal, Intratumoral
01

Overview

A combination therapy comprising **TILT-123**, an oncolytic adenovirus engineered to express human tumor necrosis factor alpha (TNFα) and interleukin-2 (IL-2); **pembrolizumab**, a monoclonal antibody targeting programmed death-1 (PD-1) to block immune checkpoint inhibition; and **pegylated liposomal doxorubicin**, a liposomal formulation of the anthracycline chemotherapeutic doxorubicin, used to increase tumor targeting and reduce systemic toxicity. This regimen is being investigated in patients with platinum-resistant or refractory ovarian cancer. TILT-123 is designed to enhance T-cell recruitment and activation within tumors as well as induce local immunogenic cell death and secondary immune priming, thereby synergizing with anti-PD-1 immunotherapy. Pembrolizumab boosts immune responses by blocking the PD-1 pathway and restoring T-cell activity against cancer cells. Pegylated liposomal doxorubicin delivers cytotoxic chemotherapy directly to tumors through nanoliposome encapsulation, minimizing toxicity to normal tissues. The combination builds on established immunomodulation and cytotoxic mechanisms, aiming for heightened efficacy, especially in immunotherapy-refractory malignancies[1][2][3][4][5].

Other names
Ad5/3-E2F-D24-hTNFα-IRES-hIL-2PLDDoxil
02

Targets

DSG2 (Desmoglein-2)IL-2 (Interleukin 2)PDCD1 (Programmed cell death protein 1 receptor)TNFA (Tumor necrosis factor alpha (soluble))TOP2A (DNA topoisomerase II)

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