Combination of Immune Checkpoint Therapy with Antibody-Drug Conjugate (ADC)

Antibody-Drug Conjugate (ADC)

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

Advantages of Combination of Immune Checkpoint Therapy With ADC

The integration of immuno-oncology combination strategies, such as the conjunction of ADCs with ICIs, represents a compelling avenue in therapeutic development. ADCs' potent cytotoxic delivery holds the potential to enhance antigen presentation by augmenting the liberation of tumor antigens from apoptotic cancer cells. Moreover, this antigen presentation process can be further amplified through direct actions of the unbound payload and the stimulation of maturation and activation in antigen-presenting dendritic cells.
The ADC-induced immunogenic cell demise (ICD) may substantially contribute to the antitumor immune response. Further enhancements in the precision of target antigen recognition and drug delivery efficacy of ADCs have the potential to refine and amplify this synergistic mechanism.

Case Study


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.
	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.
	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

Walsh, et al. "Immune checkpoint inhibitor combinations—current and emerging strategies." British Journal of Cancer 128.8 (2023): 1415-1417.
Li, Bin, et al. "Immune Checkpoint Inhibitors Combined with Targeted Therapy: The Recent Advances and Future Potentials." Cancers 15.10 (2023): 2858.
Fuentes-Antrás, Jesús, et al. "Antibody–drug conjugates: In search of partners of choice." Trends in Cancer (2023).
Boshuizen, Julia, et al. "Cooperative targeting of immunotherapy-resistant melanoma and lung cancer by an AXL-targeting antibody–drug conjugate and immune checkpoint blockade." Cancer Research 81.7 (2021): 1775-1787.

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