KAT2A is a histone acetyltransferase that functions as a transcriptional activator which, together with its paralogue KAT2B, is markedly overexpressed in acute myeloid leukemia (AML) compared to in hematopoietic progenitor cells.
Interleukin-18 (IL-18) is a pro-inflammatory cytokine that modulates innate and adaptive immune responses. Decoy-resistant IL-18, DR-18, from Simcha Therapeutics Inc., is an engineered IL-18 cytokine able to interact with the IL-18 receptor but resistant to IL-18-binding protein (IL18BP), which is a negative regulator of IL-18 signaling, thus overcoming the antitumoral efficacy limitation seen with recombinant IL-18.
Cathepsin G (CTSG) is overexpressed and aberrantly localized for antigen presentation on acute myeloid leukemia blasts and stem cells compared to normal hematopoietic progenitors. Earlier this year, Crossbow Therapeutics Inc. announced the nomination of its first development candidate, CBX-250, a TCR-mimetic (TCRm) bispecific T-cell engager (TCE) antibody targeting a CTSG peptide-human leukocyte antigen (pHLA) complex and CD3.
The lack of acute myeloid leukemia-specific antigens is one of the challenges for targeted immunotherapy together with on-target off-tumor toxicities due to the expression of the target in normal myeloid cells. A subset of T cells – Vδ2 T-cells – which represent ~5% of the T-cell population in healthy donors, are seen as part of emerging immunotherapeutic strategies.
Opna Bio AG has presented promising data regarding their EP300/CBP inhibitor OPN-6602 for the treatment of multiple myeloma (MM). The inhibition of EP300/CBP causes cell cycle arrest and apoptosis in MM cells due to suppression of interferon regulatory factor 4 (IRF4) and MYC repression.
To address the existing challenges with CAR T-cell therapy, scientists at Umoja Biopharma Inc. developed the Vivovec platform, which is an off-the-shelf surface-engineered lentiviral vector (LVV) drug product designed to generate CAR T cells in vivo without lymphodepletion by selectively binding, activating and transducing T cells.
In a presentation at the recent American Society of Hematology meeting in San Diego, Kite Pharma Inc. reported preclinical data for KITE-753, an autologous rapid manufactured anti-CD19/CD20 CAR T-cell therapy being developed for the treatment of B-cell malignancies.
At the recently concluded American Society of Hematology meeting, F Hoffmann-La Roche Ltd. presented promising results for their next-generation coagulation factor VIIIa (FVIIIa) mimetic bispecific antibody, NXT-007 (RO-7589655), supporting the ongoing phase I/II studies.
The effective targeting of RAS-mutant acute myeloid leukemia (AML) still remains a challenge; RAS mutations are tied to relapse to targeted therapy, such as resistance to FLT3 inhibitors due to the RAS/MAPK pathway, for example.
With the aim of developing an effective and more tolerable conditioning for hematopoietic stem cell transplantation (HSCT), researchers from Molecular Partners AG applied the proprietary ankyrin repeat protein (DARPin) platform to generate a novel multi-specific Switch-DARPin candidate, MP-0621.
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