" class="no-js "lang="en-US"> Tollys Releases New Preclinical Data Demonstrating Lifelong Potent Anti-tumor Immunity of TL-532 - Pharmtech Focus
Friday, January 27, 2023

Tollys Releases New Preclinical Data Demonstrating Lifelong Potent Anti-tumor Immunity of TL-532

Tollys, a biopharmaceutical company developing TL-532, the first anti-cancer immunotherapy based on a new generation of synthetic toll-like receptor 3 (TLR3) specific agonist, today announces that it will release the latest preclinical developments of TL-532 at the American Association for Cancer Research (AACR) Annual Meeting 2022.

The preclinical data included in the poster identified TL-532 as the spearhead of a new rationally designed TLR3-agonist family. In monotherapy, it demonstrated substantial tolerance and promising anti-cancer and auto-vaccinal activity, which included unrelated cancers. TL-532 also demonstrated its remarkable ability to overcome Immune Checkpoint Inhibitor (ICI) tumor-resistance, thus increasing the clinical landscape for ICI combination treatment.

Further key highlights from the poster, titled ‘The specific TLR3-agonist TL-532 induces lifelong anti-tumor auto-vaccination, cross-immunity against unrelated cancers and reverses resistance to immune checkpoint inhibitors’:

  • In vivo activity of TL-532 led to substantial tumor growth inhibition (88%) and delay (370%), translating into 35% Complete Response (CR) rate and 5.3-fold median survival benefit
  • Interestingly, among these CRs, 62% (13/21) showed life-long tumor auto-vaccination after three consecutive rechallenges at 3, 10 and 30 months
  • Remarkably, 54% (6/11) of the mice autovaccinated against bladder cancer also demonstrated cross-immunity against an unrelated and poorly immunogenic, syngeneic osteosarcoma cancer cell model (LM8)
  • TL-532 treatment appeared to decrease the expression of the immune checkpoint PD-L1 on tumor cells ex-vivo and in cDCs in vivo and demonstrated a remarkable ability to reverse the anti-PD-L1 tumor-resistance when combined with the ICI leading to doubling of CR rate
  • Ex vivo and in vivo, the tumor cell death by apoptosis induced by TL-532 was associated with a tumor microenvironment switch, evidenced by increases in antitumor biomarker secretion (IFN-α, IFN-λ1, IFN-γ, CCL5, CXCL9, CXCL10, CX3CL10), decreases in protumor biomarkers CCL22 and sFAS, and was associated in vivo with the recruitment and activation of conventional Dendritic Cells (cDCs) and Cytotoxic T-Lymphocytes (CTLs) at the tumor site.

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