Table 1.
Toll-Like Receptor 9 Agonists Recently or Currently in Development
| TLR9 Agonist | Structure | CpG Type | ROA | Tumor Types Being Evaluated |
|---|---|---|---|---|
| Cavrotolimod/AST-008 (Exicure) |
SNA with two components: (1) densely packed shell of CpG ODN radially oriented around (2) a core nanoparticle, which may be solid or hollow which facilitates increased cellular uptake | Undisclosed | IT | Melanoma; MCC; HNSCC; cSCC; advanced solid tumors |
| CMP-001 (Checkmate) |
G10 CpG ODN which forms G-quadruplex that mimics retroviral DNA encapsulated within 30 nm VLP comprised of capsid proteins derived from Qβbacteriophage known as G10 | A | SC IT |
Melanoma; NSCLC; CRC |
| CpG-28 (University of Paris) no longer in development) |
5′-TAAACGTTATAACGTTATGACGTCAT-3′ sequence with 3 CpG motifs and a fully phosphorothioate backbone | B | Intracerebral infusion | Glioma; glioblastoma |
| EnanDIM (Mologen AG) (no longer in development) |
Member of the dSLIM family exhibiting a double stem of 28 base pairs and two loops with 30 nucleotides – each containing three CG motifs – that has a linear structure | Undisclosed | SC IT |
Preclinical development |
| IMO-2055 (Idera) (no longer in development) |
Phosphorothioate sequence with two CpG ODN, synthetic immunostimulatory motifs and two 5′ ends for increased metabolic stability | B | SC IT |
Melanoma; NSCLC; CRC; HNSCC; and refractory solid tumors |
| IMO-2125/tilsotolimod) (Idera) | Phosphorothioate sequence with three CpG ODN | B | IT | Melanoma; CRC |
| MGN1703/Lefitolimod (Mologen AG) (no longer in development) |
Member of the dSLIM family exhibiting a double stem of 28 base pairs and two loops with 30 nucleotides – each containing three CG motifs – that is dumbbell-shaped and covalently-closed | Undisclosed | SC IT |
Melanoma; CRC; RCC; advanced solid tumors |
| NZ-TLR9 (LIDDS) |
Undisclosed TLR9 structure encapsulated within a calcium sulfate excipient (NanoZolid) that permits slow release depot | Undisclosed | Undisclosed | Preclinical development |
| PF‐3512676 (Pfizer) (no longer in development) |
Phosphorothioate backbone with one or more CpG dinucleotides | B | SC IV IT |
Melanoma; NSCLC; MF; CLL; CTCL; NHL |
| SD-101 (Dynavax) (no longer in development) |
30 nucleotide phosphorothioate sequence with multiple CpG motifs and internal palindromic sequences | C | SC IT |
Melanoma; lymphoma; HNSCC; prostate cancer; breast cancer; refractory solid tumors |
| S-540956 (Shionogi) |
Undisclosed | Undisclosed | Undisclosed | Preclinical development |
Abbreviations: CLL, chronic lymphocytic leukemia; CRC, colorectal cancer; cSCC, cutaneous squamous cell carcinoma; CTCL, cutaneous T cell lymphoma; dSLIM, double-stem loop immunomodulator; HNSCC, head and neck squamous cell cancer; IT, intra tumoral; IV, intravenous; MCC, Merkel cell carcinoma; MF, mycosis fungoides; N/A, not applicable; NHL, non-Hodgkin Lymphoma; NSCLC, non-small cell lung cancer; ODN, oligodeoxynucleotide; RCC, renal cell carcinoma; ROA, route of administration; SC, subcutaneous; SNA, spherical nucleic acid; VLP, virus-like particle.