HERA-CD40L / Apogenix - LARVOL DELTA

The CD40 agonist HERA-CD40L results in enhanced activation of antigen presenting cells, promoting an anti-tumor effect alone and in combination with radiotherapy. (PubMed, Front Immunol) - "Radiotherapy in combination with HERA-CD40L treatment resulted in an increase in detected intratumoral CD4+/8+ T cells compared to RT alone and, additionally, the repolarization of TAMs was also observed, resulting in an inhibition of tumor growth in a TRAMP-C1 mouse model. Taken together, HERA-CD40L resulted in activating signal transduction mechanisms in dendritic cells, resulting in an increase in intratumoral T cells and manipulation of the TME to be pro-inflammatory, repolarizing M2 macrophages to M1, enhancing tumor control."

Combination therapy • Journal • Immune Modulation • Immunology • Oncology • CD40LG • CD8 • STAT1 • TNFA

Apogenix’ new CD40 agonist HERA-CD40L significantly reduces tumor growth in prostate cancer model (PipelineReview) - "Apogenix...announced today that new preclinical data were published in the leading peer-reviewed journal Frontiers in Immunology. In the studies, Apogenix, in collaboration with the group from Professor Tim Illidge at the University of Manchester, UK, demonstrated the therapeutic benefits of the hexavalent CD40 agonist HERA-CD40L in models of prostate cancer refractory to anti-PD-1 therapies, both as monotherapy and in combination with radiotherapy. Importantly, HERA-CD40L was able to significantly reduce tumor growth through a threefold mechanism of action: it increased intratumoral T-cell concentration; modulated the tumor microenvironment (TME) towards a pro-inflammatory state; and reversed the macrophage balance from pro-tumor macrophages (tumor-associated macrophages; TAMs) to anti-tumor macrophages."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

[VIRTUAL] Generation and characterization of novel bispecific molecules combining single-chain-CD40L with anti-CEA, anti-CD95L or anti-PD-L1 targeting moieties (AACR 2021) - "CD40 ligand is a member of the TNF superfamily (TNF-SF) and a key regulator of the immune system...This clearly shows that the close proximity of anti-PD-L1 and trivalent CD40L within one molecule makes a huge difference for biological activity. Hence, these novel bispecific constructs are a promising therapeutic approach to promote anti-tumor immune responses."

IO biomarker • Oncology • CCR7 • CD40LG • CD69 • CD8 • CD86 • ICAM1 • IL2RA

The hexavalent CD40 agonist HERA-CD40L augments multi-level crosstalk between T cells and antigen-presenting cells (AACR 2018) - "The hexavalent CD40 agonist HERA-CD40L produced by the Apogenix HERA-Technology is a potent immune-regulator acting on B cells and myeloid cells. HERA-CD40L promotes activation of B cells, maturation of APC and induces an M2 to M1 phenotype switch which inhibits tolerance-inducing phagocytic activity of the repolarized macrophages in vitro. In response to CD40 ligation on APC, an efficient anti-tumor response is conferred to primary T cells through cell-cell interactions via MHC-I and CD80/CD86."

IO Biomarker • Oncology

[VIRTUAL] HERA-CD40L: A Two-Fold-Three-Based CD40 Agonist for Cancer Immunotherapy (IOS 2020) - "Treatment increases the pro-inflammatory state of all CD40-expressing cells examined and shows single-agent antitumor activity both in vitro and in vivo. The MoA has been well defined, and the biological activity has been demonstrated to be distinct from and superior to clinical benchmark “agonistic” antibodies."

Immune Modulation • Inflammation • Oncology • CD40LG

[VIRTUAL] Hexavalent HERA-CD40L induces a productive T cell-mediated anti-tumor immune response and shows superior activity in comparison to benchmark CD40 agonistic antibodies (AACR-II 2020) - "The biological activity is distinct from and superior to clinical benchmark “agonistic” antibodies. HERA-CD40L has a well-defined mechanism of action, does not depend on Fc gamma receptor-mediated crosslinking and hence functions as a true agonist."

IO Biomarker • Oncology • CD40LG

[VIRTUAL] Neutralization of pro-apoptotic CD95L by Asunercept/APG101 does not impair anti-tumor immune responses (AACR-II 2020) - "Direct co-culture of monocytes with tumor cells resulted in an M2/TAM-like phenotype which was not influenced by APG101, but re-programming to an M1-like state was achieved by addition of a CD40 agonist. Asunercept (APG101) is a potent inhibitor of pro-apoptotic/anti-proliferative CD95/CD95L signaling in immune cells and protects activated immune cells from activation induced cell death (AICD). Our results suggest that APG101 does not impair CD8 T cell activation, but rather supports their proliferation by disrupting CD95/CD95L interaction with regulatory T cells. Importantly, the primary anti-tumor killing mechanisms is most likely CD95L-independent and remains unaffected by the presence of APG101."

Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CD8 • FAS

[VIRTUAL] Novel bispecific molecules combining HERA-CD40L with anti-CEA or with anti-PD-L1 for targeting (AACR-II 2020) - "CD40 ligand is a member of the TNF superfamily and a key regulator of the immune system...As expected for an assay assessing antagonistic activities, the activity of hexavalent anti-PD-L1-HERA-CD40L was in the same range as a reference anti-PD-L1 antibody and the anti-PD-L1-trimeric scCD40L- construct. Based on the in vitro data presented, the bispecific molecules combining HERA-CD40L with tumor targeting (anti-CEA) or with a checkpoint-blockade inhibitor (anti-PD-L1) are promising therapeutic approaches to promote anti-tumor immune responses."

IO Biomarker • Oncology • CD40LG • PD-1

HERA-CD40L, a hexavalent CD40 agonist, induces a significant T cell mediated anti-tumor immune response and shows superior activity in direct comparison to benchmark agonistic antibodies (CIMT 2019) - "...Currently, seven different antibodies and only one CD40L-based hexavalent fusion protein (MEDI5083) are in active clinical trials...We performed extensive comparisons to multiple benchmark antibodies in development (including CP-870,893/Selicrelumab)...In summary, HERA-CD40L is a potent agonist able to shows single agent anti-tumor activity both in vitro and in vivo. The MoA is well defined and the biological activity is distinct from and superior to clinical benchmark “agonistic” antibodies."

IO Biomarker

HERA-CD40L, a hexavalent CD40 agonist, induces a significant T cell mediated anti-tumor immune response and shows superior activity in direct comparison to benchmark agonistic antibodies (CIMT 2019) - "...Currently, seven different antibodies and only one CD40L-based hexavalent fusion protein (MEDI5083) are in active clinical trials...We performed extensive comparisons to multiple benchmark antibodies in development (including CP-870,893/Selicrelumab)...In summary, HERA-CD40L is a potent agonist able to shows single agent anti-tumor activity both in vitro and in vivo. The MoA is well defined and the biological activity is distinct from and superior to clinical benchmark “agonistic” antibodies."

IO Biomarker

HERA-CD40L a hexavalent CD40 agonist induces T cell mediated anti-tumor immune response and shows superior activity in direct comparison to benchmark agonistic antibodies (AACR 2019) - "Comparison of HERA-CD40L to anti-CD40 benchmark antibodies (including CP-870,893) revealed superiority for HERA-CD40L in all assays tested. In addition mHERA-CD40L showed single agent anti-tumor activity in the CD40-negative syngeneic MC38-CEA mouse model, suggesting an involvement of the immune system in controlling tumor growth.In summary HERA-CD40L is a potent agonist able to establish single agent anti-tumor immune responses. Comparison to bivalent benchmark antibodies showed superior biological activity of HERA-CD40L and qualifies this molecule as an ideal candidate for combinatorial cancer treatments."