Researchers at DEM Biopharma Inc. reported preclinical findings demonstrating the efficacy of DEM-301, a bifunctional antibody-drug conjugate (ADC) engineered to selectively recognize and eliminate tumor cells that express DEM-TXX.
The University of Washington has divulged antibody-drug conjugates (ADCs) comprising an antibody targeting HER2 (erbB2) linked to monomethyl auristatin E (MMAE) through a linker. They are described as useful for the treatment of cancer.
Unlike patients with HER2+ tumors, there is an unmet clinical need for patients with HER2-low expression cancers, which are refractory to trastuzumab. Sanofi SA has developed TPP-45142, a T-cell engager consisting of two nanobody domains targeting HER2 and T-cell receptor (TCR) fused to an Fc region harboring the F234A and L235A mutations to inhibit effector function.
GT Biopharma Inc. has filed an IND application with the FDA for GTB-5550 TriKE, a B7-H3-targeted natural killer (NK) cell engager for the treatment of B7-H3-expressing solid tumor cancers. Pending approval, the planned phase I basket trial will evaluate GTB-5550 administered subcutaneously in solid tumors.
Medicenna Therapeutics Corp. is advancing MDNA-113, a first-in-class, IL-13-directed and conditionally activated PD-1 x IL-2 bifunctional superkine, through preclinical development toward a planned IND filing in the second half of this year.
CAR T cells have made headlines for their ability to fight hematological cancers, but they have proven largely ineffective against solid tumors. To fight such tumors, many groups have engineered T cells to carry T-cell receptors (TCRs) that target cancer antigens, but this approach requires using T cells taken from the patient and it is ineffective against parts of the tumor that have lost expression of the target antigen. As an alternative strategy, researchers at Zelluna ASA in Norway have engineered natural killer (NK) cells to express TCRs against solid tumor antigens.
CD276, also known as B7-H3, is an antigen highly expressed in several cancer types, including hepatocellular carcinoma (HCC, 79%-94% expression) and closely tied to aggressiveness and poor survival, but shows very low expression in normal tissues. Increasing evidence exists indicating B7-H3 has immune inhibitory functions, thus reducing interferon levels released by T cells and suppressing cytotoxic activity of natural killer cells, thereby aiding in tumor immune evasion.
Bispecific T-cell engagers (TCEs) aim to combat cancer by simultaneously binding T cells and tumor cells in order to induce the first to kill the second. This approach has failed to work effectively against many solid tumors because the exogenous engager proteins do not penetrate into tumors at sufficiently high concentrations.
Tahoe Therapeutics and Alloy Therapeutics Inc. are forming a jointly seeded new company focused on developing first-in-class antibody-drug conjugates (ADCs) for patients with hard-to-treat cancers. The joint venture will advance two ADC programs directed at novel tumor targets discovered by Tahoe using its proprietary Mosaic platform and large-scale, perturbative single-cell datasets.
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