In 2024, the field of tumor immunotherapy has been dynamic, with multiple pharmaceutical giants continuing to invest heavily in the TIGIT (T cell immunoreceptor with immunoglobulin and ITIM domains) target. Although some Phase III studies have encountered setbacks, recent positive data from the combination of Tiragolumab (anti-TIGIT monoclonal antibody) with Atezolizumab (anti-PD-L1) in the treatment of PD-L1 high-expressing non-small cell lung cancer have reignited industry hopes for TIGIT as a next-generation immune checkpoint inhibitor.

Targeted therapy against Interleukin-9 Receptor (IL-9R) has achieved a major breakthrough in the field of autoimmunity. AnaptysBio, a US-based company, announced the success of its Phase II study of the anti-IL-9R monoclonal antibody Imsidolimab for the treatment of moderate-to-severe Ulcerative Colitis (UC). This study suggests that blocking IL-9R not only directly inhibits inflammation but may also function by repairing intestinal barrier integrity.

At the American Society of Clinical Oncology (ASCO) Annual Meeting in June 2024, Phase II data for the Fibroblast Activation Protein (FAP)-targeted Radioligand Therapy ¹⁷⁷Lu-FAP-2286 (NovoFib) were presented. This therapy demonstrated favorable tolerability and encouraging antitumor activity in various advanced solid tumors (e.g., pancreatic cancer, breast cancer), particularly showing partial responses in the highly treatment-resistant sarcomatoid carcinoma and chemotherapy-refractory patients, bringing new hope for FAP-targeted therapies.As a core molecule in tumor stroma regulation, the unique expression and multifaceted functions of the FAP target within the tumor microenvironment are becoming a research hotspot. Let's explore further.

At the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, preliminary clinical data from a phase I/II study of JST-TFR09, a fully human monoclonal antibody targeting transferrin receptor 1 (TFR1), was presented. The antibody showed a manageable safety profile and preliminary anti-tumor activity in patients with relapsed/refractory acute myeloid leukemia (AML) and diffuse large B-cell lymphoma (DLBCL), achieving an objective response rate (ORR) of 35%. As a key molecular link between cellular metabolism and proliferation, let's explore the TFR1 target.

Huntington's disease is caused by a dominant mutation in the first exon of the Huntingtin (HTT) gene on chromosome 4. Specifically, it involves the expansion of the CAG trinucleotide repeat sequence beyond 35 repetitions. This leads to an abnormal elongation of the encoded polyglutamine (polyQ) chain, forming a mutant Huntingtin protein (mHTT). mHTT accumulates abnormally within neurons, forming inclusions that disrupt cellular functions and ultimately lead to neuronal death. Research has shown that a higher number of CAG repeats is associated with an earlier age of onset and more severe disease progression.