Elimination Therapies: Modalities Converging on a Single Goal
The defining therapeutic ambition of SDDS 2026: don’t manage disease — eliminate its cellular root causes. This comparison tracks the convergence of multiple modalities toward durable, potentially curative outcomes across cancer, autoimmunity, and beyond.
Modality Comparison
| Modality | Mechanism | Key Example | Target Disease | Response | Session |
|---|---|---|---|---|---|
| CAR-T (CD19) | Deep B-cell depletion → naive repopulation | Tisagenlecleucel, Axi-cel | B-cell malignancies | 46/48 CR lasted >10 years (Rosenberg melanoma TIL) | V |
| CAR-T (BCMA) | Plasma cell elimination | Carvykti (anito-cel pending) | Multiple myeloma | ~Half show functional cure; anito-cel: 96% ORR, 74% CR | II, IX |
| CAR-T (dual GBM) | OR-gate EGFR-vIII + IL-13Rα2 | Penn GBM trial | Glioblastoma | 13/18 MRI responses; best: 34 mo no recurrence | V |
| CAR-T (immune reset) | B-cell ablation → immune reboot | CD19 CAR for lupus | SLE, scleroderma | Drug-free remission >3 years | V, IX |
| T-cell engager | BCMAx CD3 bispecific | Tecvayli | Multiple myeloma | 85% long-term survival 2L; 55-day FDA approval | II |
| T-cell engager (autoimmune) | BCMAx CD3 SubQ | Gamgertamig (Gilead) | Autoimmune diseases | Single-cycle deep B/plasma depletion | IX |
| Neoantigen TIL | Selected neoantigen-reactive TIL | Rosenberg selected TIL | Solid epithelial cancers | ~24% RECIST response in chemorefractory | V |
| Shared-mutation TCR | KRAS/p53 hotspot TCR libraries | NCI TCR program | Pancreatic, colorectal | Tumor regression on KRAS G12V, p53 R175H | V |
| CELMoD (degrader) | Dual protein degradation | BMS-986470 (ZBTB7A + WIZ) | Sickle cell disease | AI-designed; preclinical | IX |
| BioPROTAC | Designed protein → FBOX → proteasomal clearance | Baker tau bioPROTAC | Alzheimer’s / tauopathies | Complete tau clearance from cells | XII |
| Drug-eluting device | Intravesical gemcitabine | Inlexzo (J&J) | Bladder cancer (NMIBC) | >80% complete response | II |
| Oral peptide (cyclic) | IL-23 receptor blockade | Icotrokinra (Icotide) | Autoimmune (psoriasis, IBD) | Five-of-five positive Phase 3 trials | II |
Three Paradigms of Elimination
1. Kill the Pathogenic Cell
The oncology paradigm: find the cell, kill it. Increasingly also applied to autoimmunity (kill pathogenic B cells, let naive ones regrow).
- CAR-T in blood cancers
- T-cell engagers (Tecvayli, Talvey)
- Neoantigen-targeted TIL for solid tumors
- CD19 CAR for immune reset in lupus
2. Degrade the Pathogenic Protein
The molecular-level paradigm: if you can’t kill the cell, clear the protein driving disease.
- CELMoDs (BMS) — small molecule degraders
- BioPROTACs (Baker) — designed protein degraders
- RIPTAC (Halda/J&J) — engage essential proteins instead of E3 ligase
3. Restore the Normal Program
The repair paradigm: don’t suppress pathology — reactivate endogenous repair.
- TIE2 agonism for retinal vascular repair (Tiespectus)
- Wnt/Frizzled-4 for blood-retinal barrier rebuilding (Restoret)
- Finerenone for cardiac remodeling (Bayer)
Why “Elimination” Is New
The shift is philosophical, not just pharmacological:
- Old paradigm: Chronic management. Symptom control. Lifetime dosing. “Disease modification.”
- New paradigm: Root-cause eradication. Drug-free remission. Potential cure. “Disease elimination.”
The word “cure” appeared more frequently at SDDS 2026 than at any previous edition — applied to myeloma (CAR-T), lupus (immune reset), melanoma (TIL), and even Alzheimer’s (Baker’s designed proteases for tau clearance).
Cross-References
- CAR-T therapy — modality hub
- Immune Reset — autoimmunity paradigm
- Neoantigen Therapy — solid tumor approach
- CAR-T Generations — design evolution
- Multiple Myeloma — elimination success story
- Lupus — immune reset case study
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