CD33 and C-type lectin-like molecule-1 (CLL-1) (CD33/CLL-1)

AML-associated cell surface antigens targeted by SparX proteins primarily include CD33 (Siglec-3) and CLL-1 (CLEC12A). These antigens are highly expressed on the surface of AML blasts and leukemic stem cells (LSCs), making them ideal targets for directed therapies (PubMed: 28232599). The SparX (Small Protein-assisted Receptor Crosslinking) platform, developed by Soteria Biotherapeutics, utilizes bispecific adapter proteins that bind these AML antigens and subsequently recruit T-cell engagers to the tumor site (Soteria Biotherapeutics). This approach aims to enhance the specificity and safety of T-cell therapies by allowing for controlled activation and reducing systemic toxicity. CD33 is a well-validated target in AML, involved in myeloid cell adhesion and signaling (UniProt P20248), while CLL-1 is a more recent target that is absent on normal hematopoietic stem cells, potentially offering a wider therapeutic window (UniProt Q5QGZ9). By targeting these antigens, SparX-based therapies facilitate the immunological destruction of leukemic cells while sparing healthy tissues. The modular nature of the SparX system allows for the fine-tuning of T-cell activity, addressing challenges like cytokine release syndrome and on-target off-tumor effects.

Other names

AML-associated cell surface antigens bound by SparX proteinsCD33CLL-1CLEC12ASiglec-3C-type lectin domain family 12 member AMICLMyeloid inhibitory C-type lectin-like receptor

T-cell redirection and activation via bispecific adapter binding to cell surface antigens, facilitating immunological destruction of leukemic cells.