The distinctive composition of ADCs, comprising an antibody (or antibody fragment), a chemical linker, and a cytotoxic payload, confers upon this category of therapeutic biological agent not only precision in target recognition but also formidable potency. The integration of immune checkpoint therapy with ADCs in combination strategies has the potential to bolster antineoplastic efficacy. The implicated mechanisms are diverse, encompassing the induction of immunogenic cell demise, maturation of dendritic cells, augmentation of T lymphocyte infiltration, as well as the amplification of immunological memory and the expression of immune-regulatory molecules, including programmed death ligand (PD-L)1 and MHC.
Fig. 1 Advancements in immune checkpoint inhibitor (ICI) combination therapy, including ADCs.1
Fig. 2 Current effective approaches: synergizing ICIs and targeted drugs.2 Considering immune checkpoint inhibitors (ICIs) as an exemplary illustration of immune checkpoint therapy has achieved notable advancement. Contemporary investigations have revealed that amalgamating ICIs with precision-targeted pharmaceuticals represents a prospective tactic for certain malignancies. This comprehensive review initially surveys the current landscape of research regarding the synergy between ICIs and targeted pharmaceuticals within the context of solid tumor treatment. This assessment encompasses an exploration of the underlying mechanisms, clinical outcomes, adverse effects, and prospective predictive biomarkers. Furthermore, it offers an outlook on future directions and potential therapeutic modalities within the domain of immunotherapy for solid tumors. |
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Fig. 3 Basis for combination therapies using antibody-drug conjugates (ADCs).3 In this current investigation, authors have formulated a synergistic approach through the integration of in situ tumor vaccination, gene-mediated suppression of tumor angiogenesis, and anti-PD-L1 therapy. |
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Fig. 4 In vivo augmentation of ICB efficacy by AXL-targeted ADCs in human melanoma and lung cancer models.4 An antibody-drug conjugate (ADC) directed at the receptor tyrosine kinase AXL exhibits pronounced efficacy against tumors, demonstrating refractoriness to immunotherapy or tumor-specific T cells across numerous melanoma and lung cancer models. Our discoveries suggest that the pursuit of AXL-targeting ADCs in immunotherapy-resistant tumor contexts fosters an immune-activating milieu within the tumor microenvironment and augments responsiveness to immune checkpoint blockade (ICB), underscoring the necessity for additional exploration of this therapeutic synergy. |
Creative Biolabs is professional in this field, offering comprehensive support for diverse drug development initiatives pertaining to immune checkpoints. Presently, an array of tailored solutions for the integration of immune checkpoint therapy with ADC is accessible through Creative Biolabs, encompassing, but not limited to: Immune Checkpoint Antibody Development, Immune Checkpoint Assays, Immune Checkpoint Targeted Peptide Development, etc. Please contact us for comprehensive information.
References
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