Immunostimulatory ADCs (iADCs), also known as immune-stimulating antibody conjugates (iSACs), are an advanced form of targeted cancer therapy. They not only activate innate immunity but also stimulate adaptive immunity, providing a dual therapeutic effect to eliminate tumor cells. They combine the specific targeting ability of antibodies with a specific immunostimulant.
DOI:10.1016/j.phrs.2024.107160
Just last week, a study by Mersana Therapeutics demonstrated the potential of their STING (STimulator of InterferoN Genes) agonist iADCs. The STING pathway is a critical component of anti-viral and anti-tumor innate immune responses. Tumor cell-directed STINGa ADCs activate STING in tumor cells and myeloid cells. Administration in mice leads to STING activation in tumors, with increased anti-tumor activity and reduced serum cytokine elevations compared to a free STING agonist. These findings reveal an important role for type III interferons in the anti-tumor activity elicited by STING agonism.
Meanwhile, other biopharmaceutical companies have been developing iADCs both in preclinical and clinical trials, including:
Preclinical: Bolt Biotherapeutics, Inc. ’s BDC-4182 targeting Claudin 18.2
Phase 1: Tallac Therapeutics’s TAC-001 to activate B cells to drive an anti-tumor immune response
A recent paper by Fu et al. (2024) describes the various clinical applications and challenges for iADCs. A major challenge is achieving the right balance of agonist potency and dosage, with severe side effects or lower efficacy being the consequences. A solution could be combining immune stimulants with other therapeutic agents to improve tumor targeting and immune response without excessive toxicity. Future developments may involve refining antibody selection, considering both penetration ability and affinity, and closely monitoring immune-related adverse events in clinical trials to improve the therapeutic window of iADCs.
This report aims to explore the events and trends of the biopharmaceutical industry in Q2 (April, May, June). Besides crovalimab and Vyloy, two more novel antibody drugs have been approved this year
These past few weeks, several antibody drug startups have progressed from the pre-seed stage to final funding rounds. In the pre-seed stage, the focus is on early research, often funded by founders, grants, or angel investors. As the company progresses to the seed stage, it seeks additional funding to validate its scientific concept and develop initial prototypes, attracting early-stage venture capital.
In August, the US FDA approved Galderma’s Nemluvio (nemolizumab) for adult patients living with prurigo nodularis (PN). Nemluvio is the first approved monoclonal antibody specifically inhibiting the signaling of IL-31, a neuroimmune cytokine that drives multiple disease mechanisms in (PN). Prurigo nodularis is a chronic skin condition that affects approximately 181,000 patients in the United States
Anti-drug antibodies (ADAs) are immune system proteins that can develop in response to therapeutic drugs, particularly biologics like monoclonal antibodies. These biopharmaceuticals have significantly advanced therapies for cancer and autoimmune diseases, but their long-term use can elicit immunogenicity due to repeated administration. The host immune system may recognize epitopes in the biologic drug as foreign, triggering the production of ADAs. This can lead to the formation of drug–ADA immune complexes, which accelerate drug clearance and potentially neutralize the drug's efficacy.
