On April 10, 2021 Tallac Therapeutics, Inc., a privately held biopharmaceutical company harnessing the power of innate and adaptive immunity to fight cancer, reported the first presentation of preclinical data demonstrating potent single-agent anti-tumor activity in preclinical cancer models with systemically administered TAC-001, the company’s lead clinical candidate from its novel Toll-like Receptor Agonist Antibody Conjugate (TRAAC) platform (Press release, Tallac Therapeutics, APR 10, 2021, View Source [SID1234577853]). The data will be presented today as part of the Immunomodulatory Agents and Interventions Session at Week I of the American Association of Cancer Research’s (AACR) (Free AACR Whitepaper) 2021 Virtual Annual Meeting (#AACR21) taking place April 10-15, 2021.
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Toll-like receptor (TLR) agonists are a novel class of immunotherapy that generate both an innate and adaptive immune response which may produce more robust and durable anti-cancer immunity to help overcome resistance to standard-of-care oncology treatments. TLR9 is a key intracellular TLR present in broad immune cell populations such as B lymphocytes and myeloid cells. Recent studies have shown that the likelihood of patients responding to immune checkpoint inhibitor therapy may depend on B cells in the tumor.i B cells play pivotal roles in the immune defense system, which bridge the innate and the adaptive immunities against cancers.ii In preclinical studies, the activation of TLR9 in human and mouse models drives B cell proliferation and differentiation.iii
"The results presented today at AACR (Free AACR Whitepaper) elucidate the unique properties of TAC-001 responsible for integrating B cells and TLR9 activation which trigger innate and adaptive immune responses to create potent, systemically delivered anti-tumor immunity across solid tumor types," said Dr. Hong I. Wan, president, CEO and co-founder of Tallac Therapeutics. "The emerging data on TAC-001 continues to strengthen our understanding of the roles that B cells and TLR9 activation play in eliciting anti-tumor immunity in checkpoint inhibitor resistant and refractory settings and will help guide our clinical development strategy."
In the e-poster, titled "TAC-001, a toll-like receptor 9 (TLR9) agonist antibody conjugate targeting B cells, promotes anti-tumor immunity and favorable safety profile following systemic administration in preclinical models," investigators present data providing evidence that in vitro targeted delivery of TAC-001 leads to superior TLR9 activation in B cells, increased expression of co-stimulatory molecules and cross-presentation leading to T cell proliferation. In vivo, TAC-001 demonstrated robust, curative and durable single agent anti-tumor activity in checkpoint inhibitor resistant and refractory tumor models. Additionally, the systemic administration of TAC-001 was shown to trigger both innate and adaptive immunity by increasing B cell infiltration, T effector cell functions and modulation in suppressive myeloid cells within the tumor microenvironment. These results support the development of TAC-001 for a broad range of solid tumor malignancies.
AACR Poster Presentation Details:
Title: TAC-001, a toll-like receptor 9 (TLR9) agonist antibody conjugate targeting B cells, promotes anti-tumor immunity and favorable safety profile following systemic administration in preclinical models
Session Type: E-Poster Session
Session Category: Immunology
Session Title: Immunomodulatory Agents and Interventions
Track: Immunology, Clinical Research Excluding Trials
Permanent Abstract Number: 1721
About TAC-001
TAC-001 is a Toll-like Receptor Agonist Antibody Conjugate (TRAAC) comprised of a potent Toll-like Receptor 9 agonist (T-CpG) conjugated to an anti-CD22 antibody, a receptor restricted to B cells. TAC-001 is designed to systemically deliver T-CpG to B cells by binding to CD22, leading to internalization of TAC-001, TLR9 signaling, B cell activation and a cascade of immune reactions. Preclinical studies demonstrate that the innate and adaptive immune responses triggered by TAC-001 leads to potent anti-tumor activity. TAC-001 is being developed to systemically deliver targeted immune activation in solid tumor cancers.