Isolating human antibody against human hepatocellular carcinoma by guided-selection

Bao, Gup-qiang; Yu, Li; Ma, Qin; He, Xianli; Xing, Jianyu; Yang, Xiang-Min; Chen, Zhi‐Nan

doi:10.4161/cbt.4.12.2273

Cited by 13 publications

(5 citation statements)

References 27 publications

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“…This polymer is very interesting for its surface properties because thanks to its quaternary ammonium groups and the strong positive charge, it can form stable complexes with anionic compounds such as drugs, proteins and DNA fragments that can be utilized for HCC liver-targeting. Monoclonal antibodies specific to tumor antigens or tumor-associated antigens represent a new opportunity for the treatment of tumors: for example, mouse monoclonal antibodies against HCC have been used for tumor imaging and targeting [95]. However possible problems are clinical toxicity and high immunogenicity that can induce the production of human anti-mouse antibodies.…”

Section: Nnn-trimethyl/alkyl Chitosansmentioning

confidence: 99%

Chitosan Nanoparticles for Therapy and Theranostics of Hepatocellular Carcinoma (HCC) and Liver-Targeting

et al. 2020

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Chitosan nanoparticles are well-known delivery systems widely used as polymeric carriers in the field of nanomedicine. Chitosan is a carbohydrate of natural origin: it is a biodegradable, biocompatible, mucoadhesive, polycationic polymer and it is endowed with penetration enhancer properties. Furthermore, it can be easily derivatized. Hepatocellular carcinoma (HCC) represents a remarkable health problem because current therapies, that include surgery, liver transplantation, trans-arterial embolization, chemoembolization and chemotherapy, present significant limitations due to the high risk of recurrence, to a lack of drug selectivity and to other serious side effects. Therefore, there is the need for new therapeutic strategies and for improving the liver-targeting to HCC. Nanomedicine consists in the use of nanoscale carriers as delivery systems to target and deliver drugs and/or diagnostic agents to specific organs or tissues. Chitosan and its derivatives can be successfully used in the preparation of nanoparticles that, for their peculiar surface-properties, can specifically interact with liver tumor, by passive and active targeting. This review concerns the use of chitosan nanoparticles for the therapy and theranostics of HCC and liver-targeting.

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Section: Nnn-trimethyl/alkyl Chitosansmentioning

confidence: 99%

Chitosan Nanoparticles for Therapy and Theranostics of Hepatocellular Carcinoma (HCC) and Liver-Targeting

et al. 2020

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“…This tumor antigen rarely has cross-reaction with normal liver cells, and I 131 -labeled HAb18 has been approved recently by the China State FDA (No. S20050039) as the global first bio-drug to treat HCC [10][11][12]. The role of Hab18G in tumor progression has also been studied in a variety of other tumors including those from stomach [13], prostate [14], and lung [15].…”

Section: Introductionmentioning

confidence: 99%

Expression of HAb18G is associated with tumor progression and prognosis of breast carcinoma

Liu

Cui

Zhang

et al. 2010

Breast Cancer Res Treat

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HAb18G is a recently identified hepatoma-associated antigen and its association with tumor growth, invasion, and angiogenesis has been studied in a variety of tumors. However, its role in the tumor progression of breast cancer has not been explored. HAb18G expression was examined by immunohistochemistry in pathological sections of 1,637 breast tissue samples and by in situ hybridization in 41 cases of invasive breast carcinomas (BC). While not detected in any cases of tumor-like conditions or benign tumors of breast, and only rarely in normal tissue (4.4%), HAb18G expression was gradually up-regulated from atypical ductal hyperplasia (27.3%), to ductal carcinoma-in situ (59.8%), and to BC (61.4%) (P < 0.01). Its expression in BC was correlated positively with C-erbB-2 expression and histologic grade (P < 0.001), and negatively with the expression of estrogen and progesterone receptors (P < 0.001). Significant differences of expression were also identified among the subgroups of BC examined: in decreasing order from invasive micropapillary carcinoma, ductal carcinoma, lobular carcinoma, papillary carcinoma, medullary carcinoma, to mucinous adenocarcinoma (P = 0.001), corresponding to their known clinical aggressiveness. In an expanded group of 186 BC patients with proper follow up, our previous findings were confirmed: HAb18G expression was significantly associated with local recurrence, distant metastasis and tumor mortality (P < 0.01). We also demonstrated that up-regulated tumor expression of HAb18G was a significant predictor of reduced disease progression-free survival rate and a shorter overall survival, independent of systemic therapies. In conclusion, this study suggests that HAb18G expression is associated with BC progression and prognosis. Further evaluation of this new marker in breast cancer is indicated.

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“…Numerous studies have shown that VH-VL pairing in conventional antibodies is promiscuous ( 63 – 65 ) although analysis of a large dataset of antibodies showed that VH–VL pairing does not occur at random ( 66 ). Formation of antigen binding Fvs by heterologous pairing of mouse and human variable domains has also been used for humanization of rodent antibodies by guided selection ( 67 , 68 ). Mispairing of antibody light chains is also often observed during single-cell production of bispecific antibodies ( 69 ).…”

Section: Discussionmentioning

confidence: 99%

Serum immunoglobulin or albumin binding single-domain antibodies that enable tailored half-life extension of biologics in multiple animal species

Harmsen,

Ackerschott,

de Smit

2024

Front. Immunol.

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Single-domain antibody fragments (sdAbs) can be isolated from heavy-chain-only antibodies that occur in camelids or the heavy chain of conventional antibodies, that also occur in camelids. Therapeutic application of sdAbs is often complicated by their low serum half-life. Fusion to sdAb that bind to long-lived serum proteins albumin or IgG can prolong serum half-life of fusion partners. Such studies mostly focused on human application. For half-life prolongation in multiple animal species novel species cross-reacting sdAb are needed. We here describe the isolation from immunized llamas of sdAbs G6 and G13 that bound IgG of 9-10 species analysed, including horse, dog, cat, and swine, as well as sdAb A12 that bound horse, dog, swine and cat albumin. A12 bound albumin with 13 to 271 nM affinity dependent on the species. G13 affinity was difficult to determine by biolayer interferometry due to low and heterogeneous signals. G13 and G6 compete for the same binding domain on Fab fragments. Furthermore, they both lack the hallmark residues typical of camelid sdAbs derived from heavy-chain antibodies and had sequence characteristics typical of human sdAbs with high solubility and stability. This suggests they are derived from conventional llama antibodies. They most likely bind IgG through pairing with VL domains at the VH-VL interface rather than a paratope involving complementarity determining regions. None of the isolated sdAb interfered with FcRn binding to albumin or IgG, and thus do not prevent endosomal albumin/IgG-sdAb complex recycling. Fusions of albumin-binding sdAb A12 to several tetanus neurotoxin (TeNT) binding sdAbs prolonged the terminal serum half-life in piglets to about 4 days, comparable to authentic swine albumin. However, G13 conferred a much lower half-life of 0.84 days. Similarly, in horse, G13 prolonged half-life to only 1.2 days whereas A12 fused to two TeNT binding domains (T6T16A12) had a half-life of 21 days. The high half-life of T6T16A12, which earlier proved to be a highly potent TeNT antitoxin, further supports its therapeutic value. Furthermore, we have identified several additional sdAbs that enable tailored half-life extension of biologicals in multiple animal species.

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Isolating human antibody against human hepatocellular carcinoma by guided-selection

Cited by 13 publications

References 27 publications

Chitosan Nanoparticles for Therapy and Theranostics of Hepatocellular Carcinoma (HCC) and Liver-Targeting

Chitosan Nanoparticles for Therapy and Theranostics of Hepatocellular Carcinoma (HCC) and Liver-Targeting

Expression of HAb18G is associated with tumor progression and prognosis of breast carcinoma

Serum immunoglobulin or albumin binding single-domain antibodies that enable tailored half-life extension of biologics in multiple animal species

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