AXL positive

P1/2, N=42, Not yet recruiting, Shanghai Zhongshan Hospital

AXL expression is associated with reduced immunotherapy efficacy in NSCLC and may serve as a predictive biomarker and therapeutic target.

While AB-329 demonstrated moderate antiproliferative effects as a monotherapy, its combination with paclitaxel led to substantially enhanced antiproliferative and anti-metastatic effects compared to gemcitabine, DXd, and SN-38. Analysis of human breast cancer tissue further confirmed that low AXL expression is associated with a higher presence of NK cells in the tumor. These findings suggest that AB-329 not only augments chemotherapy efficacy but also reshapes the tumor immune microenvironment, supporting its further development as a dual-action therapeutic strategy for AXL-positive TNBC.

In summary, our data suggest that axl-miR-214sponge is specific, effective and safe in blocking axl-positive cancer cell spreading. Thus, it represents a promising targeted therapy tool to fight metastasis.

Furthermore, in nonhuman primates, mecbotamab vedotin demonstrated excellent tolerability at doses of up to 5 mg/kg and maintained linker-payload stability in vivo. These findings indicate that mecbotamab vedotin has the potential to be a robust and less toxic therapeutic agent, offering promise as a treatment for patients with AXL-positive cancers.

In vivo, four administrations of mfhAXL CAR-T cells suppressed tumor growth without body weight loss. The mRNA-electroporated mfhAXL CAR-T platform enables cost-effective, large-scale production, offering a safer alternative to viral vector-based approaches by eliminating risks of insertional mutagenesis and immunogenicity.

demonstrate superior therapeutic efficacy of Gilteritinib, a FDA-approved small-molecule inhibitor, in the AXL-expressing esophageal cancer, ovarian cancer and gastric cancer cell lines, PDXOs and PDXs models. This work highlights Gilteritinib as a novel and potent therapeutic approach for the treatment of AXL-positive solid tumors.

Moreover, ZAXL:239 was found to have significant anti-tumor effects in AXL-positive GC transplantation tumor nude mouse models. In brief, we provide strong evidence that the novel ZAXL:239 affibody molecules have great potential as a potent tumor-specific molecular imaging and targeted therapeutic agents for GC.

P1, N=9, Terminated, Shanghai PerHum Therapeutics Co., Ltd. | Trial completion date: Aug 2025 --> Oct 2024 | Recruiting --> Terminated; Adjustment of study strategy

Using these in vitro models, its anti-tumor effect was evaluated as a single agent, and in combination with standard of care agents venetoclax or cytarabine. Because of their diagnostic potential, sdAbs could be used to screen patients eligible for AXL-targeted therapy and to follow-up AXL expression during treatment and disease progression. When fused to an Fc-domain, sdAbs acquire additional therapeutic properties that can lead to a multidrug approach for the treatment of AXL-positive cancer patients.

Notably, we found the anti-AXL CAR-NK cells could inhibit the BRAFi-resistant melanoma growth and metastasis in vivo preclinical mouse models. Conclusions Our findings propose that Anti-AXL CAR-NK cell immunotherapy is a promising approach to target BRAF inhibitor drug-resistant and metastatic melanoma.

Analysis is ongoing to define spatial intratumoral, intranodal, and geographic intertumoral heterogeneity. Our data provide mechanistic insight to the potential for macrophage-specific and AXL-directed therapy to improve immunotherapeutic response and further exploration of potential as a predictive biomarker is warranted.