Antibody-drug conjugates targeting DDR1 as a novel strategy for treatment of breast cancer.

Antibody-drug conjugates (ADCs) have emerged as a novel class of targeted cancer therapies and been successfully applied in the treatment of breast cancer (BC). Discoidin domain receptor 1 (DDR1) is a single transmembrane receptor tyrosine kinase and has been identified as a possible target for cancer. In this study, we explored the potential of an anti-DDR1 ADC, named TH-DM4, for the treatment of DDR1-positive BC.

Discovery and mechanistic insights into thieno[3,2-d]pyrimidine and heterocyclic fused pyrimidines inhibitors targeting tubulin for cancer therapy.

Guided by the X-ray cocrystal structure of the lead compound 4a, we developed a series of thieno[3,2-d]pyrimidine and heterocyclic fused pyrimidines demonstrating potent antiproliferative activity against four tumor cell lines. Two analogs, 13 and 25d, exhibited IC values around 1 nM and overcame P-glycoprotein (P-gp)-mediated multidrug resistance (MDR). At low concentrations, 13 and 25d inhibited both the colony formation of SKOV3 cells in vitro and tubulin polymerization.

Emerging trends in small molecule inhibitors targeting aldosterone synthase: A new paradigm in cardiovascular disease treatment.

Aldosterone synthase (CYP11B2) is the rate-limiting enzyme in aldosterone production. In recent years, CYP11B2 has become an appealing target for treating conditions associated with excess aldosterone, such as hypertension, heart failure, and cardiometabolic diseases. Several small-molecule inhibitors of CYP11B2 have demonstrated efficacy in both preclinical studies and clinical trials.

Non-IL-2-blocking anti-CD25 antibody inhibits tumor growth by depleting Tregs and has synergistic effects with anti-CTLA-4 therapy.

CD25, also known as the interleukin-2 receptor α chain (IL-2Rα), is highly expressed on regulatory T cells (Tregs), but relatively lower on effector T cells (Teffs). This makes it a potential target for Treg depletion, which can be used in tumor immunotherapy. However, marketed anti-CD25 antibodies (Basiliximab and Daclizumab) were originally developed as immunosuppressive drugs to prevent graft rejection, because these antibodies can block IL-2 binding to CD25 on Teffs, which in turn destroys the function of Teffs.

FTL004, an anti-CD38 mAb with negligible RBC binding and enhanced pro-apoptotic activity, is a novel candidate for treatments of multiple myeloma and non-Hodgkin lymphoma.

Anti-CD38 monoclonal antibodies (mAbs), daratumumab, and isatuximab have represented a breakthrough in the treatment of multiple myeloma (MM). Recently, CD38-based mAbs were expected to achieve increasing potential beyond MM, which encouraged us to develop new anti-CD38 mAbs to meet clinical needs. In this study, we developed a novel humanized anti-CD38 antibody, FTL004, which exhibited enhanced pro-apoptotic ability and negligible binding to red blood cells (RBCs).

Effective antitumor activity of 5T4-specific CAR-T cells against ovarian cancer cells in vitro and xenotransplanted tumors in vivo.

Ovarian cancer is considered to be the most lethal gynecologic malignancy, and despite the development of conventional therapies and new therapeutic approaches, the patient's survival time remains short because of tumor recurrence and metastasis. Therefore, effective methods to control tumor progression are urgently needed. The oncofetal tumor-associated antigen 5T4 (trophoblast glycoprotein, TPBG) represents an appealing target for adoptive T-cell immunotherapy as it is highly expressed on the surface of various tumor cells, has very limited expression in normal tissues, and spreads widely in malignant tumors throughout their development.

Preparation and characterization of a high-affinity monoclonal antibody against nerve growth factor.

Nerve growth factor (NGF) is produced and released in injured tissues or chronic pain tissues caused by other diseases. Studies have shown that monoclonal antibodies targeting NGF have a good efficacy in the treatment of osteoarthritis (OA), low back pain and chronic pain, which may be a promising therapy. In this study, DNA sequences of NGF-his and NGF-hFc were synthesized using eukaryotic expression system and subcloned into pTT5 expression vector.

Cryptophycin-55/52 based antibody-drug conjugates: Synthesis, efficacy, and mode of action studies.

Cryptophycin-52 (CR52), a tubulin inhibitor, exhibits promising antitumor activity in vitro (picomolar level) and in mouse xenograft models. However, the narrow therapeutic window in clinical trials limits its further development. Antibody-drug conjugate (ADC), formed by coupling cytotoxic compound (payload) to an antibody via a linker, can deliver drug to tumor locations in a targeted manner by antibody, enhancing the therapeutic effects and reducing toxic and side effects.

Targeting of DDR1 with antibody-drug conjugates has antitumor effects in a mouse model of colon carcinoma.

DDR1 has been identified as a cancer-associated receptor tyrosine kinase that is highly expressed in several malignancies relative to normal tissues. Clinically approved multi-kinase inhibitors, such as nilotinib, inhibit DDR1-mediated tumor growth in xenograft models, suggesting DDR1 might be a potential target for cancer treatments. Here, we employed an antibody-based strategy with a novel anti-DDR1 antibody-drug conjugate (ADC) for colon carcinoma treatment.