차세대 항체약물접합체(ADC) : 기술 상황, 혁신 추진력, 경쟁 환경 및 세계 시장 전망(2025-2035년)

Executive Summary

The global antibody-drug conjugate (ADC) landscape is undergoing a paradigm shift from conventional cytotoxic delivery constructs to intelligent, programmable, next-generation biologic-nanomachines. Third- and fourth-generation ADCs integrate innovations in target biology, payload engineering, tumor-microenvironment-sensitive linker systems, DAR precision, internalization-independent cytotoxicity, immune-activating payloads, and bispecific/biparatopic antibody scaffolds.

These advances aim to overcome major limitations of classical ADCs:

• Heterogeneous DAR distribution & plasma instability
• Off-target toxicity & narrow therapeutic window
• Limited tumor penetration & resistant clones
• Payload saturation & restricted payload diversity

Next-gen ADCs are increasingly positioned as hybrid biologic-immunotherapeutic systems capable of:

• Tumor-targeted cytotoxicity
• Bystander killing & stromal penetration
• Immune microenvironment remodeling
• Checkpoint synergy
• Reduced systemic exposure via tumor-triggered payload release

Key scientific vectors transforming ADC modalities:

1. Conditional Activation Systems - protease, pH, ROS, hypoxia-cleavable linkers

2. Advanced Payload Platforms - TOP1 inhibitors, PBD dimers, immune-agonists, DNA-alkylators, RNA effector payloads (preclinical)

3. Multivalent & Logic-Gated Targeting - biparatopic & bispecific ADCs

4. DAR Uniformity & Site-Specific Conjugation - THIOMABs, enzymatic ligation, click-chemistry

5. Internalization-Independent Killing - extracellular payload activation

Commercial drivers include HER2-low expansion, HER3 & TROP2 momentum, CLDN18.2 surge in GI tumors, and China's emergence as the fastest-growing ADC innovation hub.

The market is forecast to grow from ~USD 10B in 2024 to > USD 70B by 2035, with >300 active clinical programs and >1,000 preclinical constructs globally. Growth will be fueled by:

• Line expansion from metastatic to early adjuvant settings
• Synergistic IO-ADC combinations
• Platform licensing economics
• Entry into non-oncology (fibrosis, autoimmune) by 2030+

This report provides a first-principles analysis of the next-decade ADC innovation engine, integrating scientific evolution with deal-flow, CDMO capacity, manufacturing constraints, regulatory precedents, clinical risk vectors, pricing and HTA modeling, and portfolio prioritization frameworks.

Table of Content

1. Introduction

• 1.1 Scope & methodology
• 1.2 Evolution of ADC field - historical to future trajectory
• 1.3 Definitions & modality segmentation (Gen 1 -> Gen 4)

2. Next-Generation ADC Technology Architecture

• 2.1 Antibody backbone engineering
  • 2.1.1 Biparatopic antibodies
  • 2.1.2 Bispecific targeting platforms
  • 2.1.3 Fc engineering for PK & ADCC enhancement
• 2.2 Linker intelligence systems
  • 2.2.1 Protease-cleavable linkers
  • 2.2.2 pH-sensitive, reduction-sensitive linkers
  • 2.2.3 Self-immolative linker systems
  • 2.2.4 Biomarker-activated release linkers
• 2.3 Payload innovations
  • 2.3.1 DNA-topoisomerase I payloads
  • 2.3.2 PBD dimers & duocarmycins
  • 2.3.3 Immune-stimulatory payloads (TLR, STING)
  • 2.3.4 Emerging RNA-toxin concepts
  • 2.3.5 Next-gen tubulin inhibitors
• 2.4 Drug-to-antibody ratio (DAR) precision engineering
• 2.5 Tumor microenvironment (TME) guided ADC design
• 2.6 Internalization-independent ADC mechanisms
• 2.7 ADC-IO combinations & rationale
• 2.8 AI in ADC design & antigen discovery
• 2.9 Pharmacokinetics, metabolism & toxicity modeling

3. Disease Landscape & Target Biology

• 3.1 HER2-low & HER2-ultralow expansion
• 3.2 HER3, TROP2, CLDN18.2, ROR1, B7-H4 targets
• 3.3 Solid tumors vs hematological cancers
• 3.4 Biomarker & companion diagnostics ecosystem

4. Clinical Development Landscape

• 4.1 Global clinical trial mapping (Phase I-III)
• 4.2 Key ongoing pivotal programs
• 4.3 Regulatory designations & accelerated pathways
• 4.4 Safety events, black-box risk, dose-limiting toxicity
• 4.5 ADC resistance mechanisms & mitigation strategies

5. Competitive Intelligence

• 5.1 Company landscape (established & emerging leaders)
• 5.2 Platform licensing ecosystem
• 5.3 China ADC innovation ecosystem & strategic dynamics
• 5.4 Key partnerships
• 5.5 SWOT of ADC modality vs IO, cell therapy, TPD

6. Commercial & Market Outlook

• 6.1 Market sizing (2024-2035)
• 6.2 Pricing benchmarks
• 6.3 Reimbursement dynamics
• 6.4 BLA case studies (Trodelvy, Enhertu, Padcev)
• 6.5 Forecast scenarios - BASE / BULL / REGULATORY-RISKED

7. Strategic Outlook

• 7.1 Next-gen platform winners
• 7.2 ADCs beyond oncology
• 7.3 M&A & pipeline prioritization heatmap
• 7.4 Technology adjacency: Radio-conjugates, Immune ADCs, ADC-bispecific hybrids

8. Appendix