Combining the direct cytotoxic effects of antibody-drug conjugates (ADCs) with the immune-enhancing properties of immunostimulators represents a new therapeutic strategy that could not only eradicate tumor cells, but also reprogram the tumor microenvironment, leading to durable and systemic anticancer immunity. Using this new approach, researchers from Bioray Pharmaceutical Co. Ltd. developed and characterized of a new dual drug ADC (BiADC), named BR-113, designed to target human (h)Trop2.
RAS G12D is one of the most frequent mutations in RAS, and when it occurs, it leaves RAS in a permanently active state, causing the cell to proliferate uncontrollably. Examples of the so-called RAS-addicted cancers are colorectal cancer or pancreatic ductal adenocarcinoma.
Immunostimulant therapy using agonistic cytokines or activating antibodies has been associated with off-target side effects, failure to preferentially activate cytotoxic lymphocytes (CTLs) over regulatory T cells (Treg), and the development of T-cell exhaustion. With the aim of overcoming these issues, researchers from Recourse Biologics Inc. designed a potentially first-in-class immunostimulatory fusion protein.
Researchers from Cedars-Sinai Medical Center presented the preclinical efficacy of KROS-401, an IL-4/IL-13 blocking peptide that effectively reprograms macrophages in glioma models.
Patients with metastatic or unresectable gastric cancer are usually given 5-fluorouracil (5-FU) and platinum-based chemotherapy, but patients with advance disease usually have a poor prognosis. The use of chemotherapy increased the levels of cyclooxygenase-2 in tumor cells, which in turn increase the levels of prostaglandin E2 (PGE2) in the tumor microenvironment. When PGE2 binds to their receptors EP1 to EP4 on immune cells, it triggers an immunosuppressive tumor microenvironment. The use of the EP2 and EP4 dual antagonist OCT-598 was tested in the preclinical setting for gastric cancer.
Tumor immune evasion mechanisms could be reversed by activating intracellular antiviral immune responses. It has been reported that the use of DNA methyltransferase (DNMT) inhibitors combined with poly(ADP ribose) polymerase (PARP) inhibitors activated stimulator of interferon genes (STING) signaling pathway in a process named pathogen mimicry response.
Mesenchymal-epithelial transition factor (MET) plays a relevant role in growth, survival, migration and tissue repair. Alterations in MET have been found in non-small-cell lung cancer and head and neck cancer, and are associated with aggressive and difficult-to-treat cancer types.
Scientists at the University of Wisconsin Madison and Dana-Farber Cancer Institute recently presented preclinical data for the radiopharmaceutical therapy candidate [177Lu]PNT-6555.
Researchers from Sichuan Baili Pharmaceutical Co. Ltd. and Systimmune Inc. presented preclinical data for the novel CD33-targeting antibody-drug conjugate (ADC) being evaluated for the treatment of hematologic malignancies.
α-Fetoprotein (AFP) is a tumor-associated antigen and an ideal target for T-cell receptor T-cell (TCR-T) therapy. While the safety of AFP-targeting TCR-T products has been previously demonstrated in early clinical trials, the efficacy of these cell therapies is still modest, warranting further research.
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