Peptide drug conjugates (PDCs) utilize the specificity of peptides to release cytotoxic loads directly to cancer cells. Alfa Cytology aims to develop targeted therapies that inhibit pancreatic tumor growth, induce apoptosis, and attenuate tumor heterogeneity using PDC technology.
Introduction to Peptide Drug Conjugates
Peptide drug conjugates (PDCs) are a class of therapeutic agents that combine the targeting specificity of peptides with the high potency of small molecule drugs. These conjugates consist of a peptide moiety attached to a small molecule drug through a linker molecule, allowing for selective delivery of the drug to specific cells or tissues. The small molecule drug in a PDC is typically a potent therapeutic agent with low bioavailability or poor target selectivity. By conjugating the drug to a peptide, its pharmacokinetic properties can be improved, leading to better therapeutic outcomes.
Fig. 1 A schematic of a peptide–drug conjugate structure. (Fu C, 2023)
Linkers Used in Peptide Drug Conjugates
The linker molecule in a PDC plays a crucial role in controlling the release of the drug at the target site. It must be stable in circulation to prevent premature release of the drug, but also cleavable under specific conditions (such as low pH or enzymatic activity) to allow for controlled drug release once the PDC reaches its target. Various types of linkers can be used depending on the desired release profile of the drug.
| Linker Type | Name |
|---|---|
| Non-cleavage | Carbon chain, Amido bond, Ether bond |
| pH sensitive | Hydrazone bond, Vinyl ether bond, Acetal/Ketal bond |
| Enzyme sensitive | Disulfide bond |
| Redox sensitive | Gly-Phe-Leu-Gly, Val-Cit (Cit=Citrulline), Phe-Lys |
Peptide Drug Conjugates Development for Pancreatic Cancer
Pancreatic cancer is one of the most lethal types of cancer with limited treatment options. However, several approved PDCs are now available for the treatment of pancreatic cancer, offering renewed hope for patients battling this aggressive disease.
| Peptide Drug Conjugates | Year Approved | Introduction |
|---|---|---|
| Pegilodecakin (AM0010) | 2017 | Pegilodecakin is a PEGylated form of interleukin-10 (IL-10) that targets the tumor microenvironment in pancreatic cancer. |
| Pasireotide-tyrosine-3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (SSTR)-conjugate | 2018 | This PDC combines pasireotide, a somatostatin analog, with a targeting peptide specifically directed against SSTR, a receptor overexpressed in pancreatic neuroendocrine tumors. |
| Gemcitabine-ABD-fibrin/hyaluronic acid-conjugate | 2019 | Through conjugation with an antifibronectin single-chain antibody fragment, this PDC specifically targets tumor-associated fibronectin overexpression, resulting in enhanced delivery of gemcitabine to the tumor site. |
