Leukocyte surface antigen CD47 and tubulin beta chain (CD47 + TUBB)

CD47 and beta-tubulin represent a therapeutic target-payload system primarily utilized in the development of antibody-drug conjugates (ADCs) and combination therapies for cancer [1, 9]. CD47, also known as integrin-associated protein (IAP), is a cell surface glycoprotein that acts as a "don't eat me" signal by interacting with SIRPα on macrophages, allowing tumor cells to evade the innate immune system [8, 14]. Beta-tubulin is a core component of microtubules, which are essential for cell division, intracellular transport, and structural integrity [2, 10]. In the ADC context, anti-CD47 antibodies are used to selectively target cancer cells and deliver tubulin-disrupting payloads, such as mertansine (DM1) or auristatins [1, 3]. Upon binding and internalization, the payload is released and binds to beta-tubulin, inhibiting microtubule polymerization or stabilization, which results in G2/M phase cell cycle arrest and apoptosis [9, 11]. Furthermore, CD47 signaling has been shown to modulate the sensitivity of cancer cells to taxane-based chemotherapies, making this combination a significant focus for treating aggressive and drug-resistant malignancies like triple-negative breast cancer and various hematologic cancers [43, 49]. Notable safety concerns include hematologic toxicities like anemia and thrombocytopenia due to CD47 expression on healthy blood cells [16, 28]. Overall, the CD47 and beta-tubulin axis offers a promising avenue for precision oncology by combining immunotherapy with targeted chemotherapy [1, 15].

Other names

CD47-targeted tubulin inhibitorIntegrin-associated protein and beta-tubulinCD47-DM1 ADC targetCD47-MMAE ADC target

Antibody-drug conjugate (ADC) targeting CD47 to deliver tubulin-inhibiting payloads; the antibody component binds to CD47 on the cell surface, leading to internalization and release of the payload which binds to beta-tubulin to disrupt microtubule dynamics and induce mitotic arrest. Additionally, CD47 signaling can modulate sensitivity to tubulin-targeting chemotherapeutics.