Tenascin C (TNC), a glycoprotein that is abundant in the tumor extracellular matrix (ECM), is strongly overexpressed in tumor tissues but virtually undetectable in most normal tissues. Many TNC antibodies, peptides, aptamers, and nanobodies have been investigated as delivery vectors, including 20A1, α-A2, α-A3, α-IIIB, α-D, BC-2, BC-4 BC-8, 81C6, ch81C6, F16, FHK, Ft, Ft-NP, G11, G11-iRGD, GBI-10, 19H12, J1/TN1, J1/TN2, J1/TN3, J1/TN4, J1/TN5, NJT3, NJT4, NJT6, P12, PL1, PL3, R6N, SMART, ST2146, ST2485, TN11, TN12, TNFnA1A2-Fc, TNfnA1D-Fc, TNfnBD-Fc, TNFnCD-Fc, TNfnD6-Fc, TNfn78-Fc, TTA1, TTA1.1, and TTA1.2. In particular, BC-2, BC-4, 81C6, ch81C6, F16, FHK, G11, PL1, PL3, R6N, ST2146, TN11, and TN12 have been tested in human tissues. G11-iRGD and simultaneous multiple aptamers and arginine–glycine–aspartic acid (RGD) targeting (SMART) may be assessed in clinical trials because G11, iRGD and AS1411 (SMART components) are already in clinical trials. Many TNC-conjugate agents, including antibody–drug conjugates (ADCs), antibody fragment–drug conjugates (FDCs), immune-stimulating antibody conjugates (ISACs), and radionuclide–drug conjugates (RDCs), have been investigated in preclinical and clinical trials. RDCs investigated in clinical trials include ¹¹¹In-DTPA-BC-2, ¹³¹I-BC-2, ¹³¹I-BC-4, ⁹⁰Y-BC4, ¹³¹I81C6, ¹³¹I-ch81C6, ²¹¹At-ch81C6, F16¹²⁴I, ¹³¹I-tenatumomab, ST2146biot, FDC ¹³¹I-F16S1PF(ab’)2, and ISAC F16IL2. ADCs (including FHK-SSL-Nav, FHK-NB-DOX, Ft-NP-PTX, and F16*-MMAE) and ISACs (IL12-R6N and ¹²⁵I-G11-IL2) may enter clinical trials because they contain components of marketed treatments or agents that were investigated in previous clinical studies. This comprehensive review presents historical perspectives on clinical advances in TNC-conjugate agents to provide timely information to facilitate tumor-targeting drug development using TNC.

腱蛋白 C (TNC) 是一种在肿瘤细胞外基质 (ECM) 中丰富的糖蛋白，在肿瘤组织中强烈过度表达，但在大多数正常组织中几乎检测不到。许多 TNC 抗体、肽、适体和纳米抗体已被研究作为递送载体，包括 20A1、α-A2、α-A3、α-IIIB、α-D、BC-2、BC-4 BC-8、81C6、ch81C6 , F16, FHK, Ft, Ft-NP, G11, G11-iRGD, GBI-10, 19H12, J1/TN1, J1/TN2, J1/TN3, J1/TN4, J1/TN5, NJT3, NJT4, NJT6, P12 、PL1、PL3、R6N、SMART、ST2146、ST2485、TN11、TN12、TNFnA1A2-Fc、TNfnA1D-Fc、TNfnBD-Fc、TNFnCD-Fc、TNfnD6-Fc、TNfn78-Fc、TTA1、TTA1.1 和 TTA1。 2.特别是，BC-2、BC-4、81C6、ch81C6、F16、FHK、G11、PL1、PL3、R6N、ST2146、TN11 和 TN12 已在人体组织中进行了测试。 G11-iRGD 和同步多个适体以及精氨酸-甘氨酸-天冬氨酸 (RGD) 靶向 (SMART) 可能会在临床试验中进行评估，因为 G11、iRGD 和 AS1411（SMART 成分）已处于临床试验中。许多 TNC 偶联剂，包括抗体-药物偶联物 (ADC)、抗体片段-药物偶联物 (FDC)、免疫刺激抗体偶联物 (ISAC) 和放射性核素-药物偶联物 (RDC)，已在临床前和临床试验中进行了研究。临床试验中研究的 RDC 包括 ¹¹¹ In-DTPA-BC-2、 ¹³¹ I-BC-2、 ¹³¹ I-BC-4、 ⁹⁰ Y-BC4， ¹³¹ I 81C6， ¹³¹ I-ch81C6， ²¹¹ At-ch81C6，F16 ¹²⁴ I、 ¹³¹ I-tenatumomab、ST2146biot、FDC ¹³¹ I-F16S1PF(ab')2 和 ISAC F16IL2。 ADC（包括FHK-SSL-Nav、FHK-NB-DOX、Ft-NP-PTX和F16*-MMAE）和ISAC（IL12-R6N和 ¹²⁵ I-G11-IL2）可能进入临床试验，因为它们含有在之前的临床研究中研究过的市售治疗或药物的成分。 这篇全面的综述介绍了 TNC 结合剂临床进展的历史观点，以提供及时的信息，促进利用 TNC 进行肿瘤靶向药物的开发。