With the development of therapeutic monoclonal antibodies, the therapeutic antibodies have increasingly dominated the global pharmacy market in recent years, which are concentrated on the treatment of carcinoma, transplant rejection, auto-immune diseases etc. Meanwhile, the therapeutic antibodies could be categorized on the humanized proportion into several different types, such as murine-derived antibody, chimeric antibody, humanized antibody and human antibody. Herein, we focused both on antibody research hot spots and humanized anti-tumor antibody drugs. Moreover, in accordance with the classical examples of humanized anti-tumor antibody drugs approved by relevant authorities worldwide, we explained the research status and situation from both the humanized technologies and production of humanized antibodies. Additionally, it seemingly rational and reasonable to demonstrate the trend of further humanized anti-tumor antibody drugs in the prospect of the present situation either domestic or overseas.
Animals ; Antibodies, Monoclonal, Humanized ; immunology ; therapeutic use ; Antineoplastic Agents ; immunology ; therapeutic use ; Humans ; Neoplasms ; therapy

The use of monoclonal antibodies (mAbs) for cancer therapy has achieved considerable success in recent years. Approximate 17 monoclonal antibodies have been approved as cancer therapeutics since 1997. Antibody-drug conjugates (ADC) are powerful new treatment options for cancer, and naked antibodies have recently achieved remarkable success. The safety and effectiveness of therapeutic mAbs in oncology vary depending on the nature of the target antigen and the mechanisms of tumor cell killing. This review provides a summary of the current state of antibody-based cancer therapy, including the mechanisms of tumor cell killing by antibodies, tumor antigens as antibody targets, clinical effectiveness of antibodies in cancer patients and nanoparticles-based ADCs.
Antibodies, Monoclonal ; immunology ; therapeutic use ; Antigens, Neoplasm ; immunology ; Antineoplastic Agents ; therapeutic use ; Humans ; Immunoconjugates ; therapeutic use ; Nanoparticles ; Neoplasms ; immunology ; therapy

Tumor surface antigen human epidermal growth factor receptor 2 (Her2) is a type I receptor tyrosine kinase, which belongs to human epidermal growth factor receptor family. Her2-overexpression is associated with tumorigenesis and metastasis. Due to significant clinical effects, Her2-targeted cancer therapy especially therapeutic antibody has become the hot spot in the field of cancer treatment. Anti-Her2 antibody drugs include monoclonal antibodies, antibody-drug conjugates, bispecific antibodies and emerging "two in one" antibody. Based on structure and function of Her2, this review focuses on recent advances in active mechanisms and clinical researches of these antibodies.
Antibodies, Bispecific ; therapeutic use ; Antibodies, Monoclonal ; therapeutic use ; Humans ; Immunoconjugates ; therapeutic use ; Neoplasms ; drug therapy ; Receptor, ErbB-2 ; immunology

BACKGROUNDImmunosuppression for immunologically high-risk kidney transplant patients usually involves antithymocyte globulin induction with triple drug maintenance therapy. Alemtuzumab, a humanized anti-CD52 antibody, was expected to be a promising induction therapy agent for kidney transplantation. However, currently no consensus is available about its efficacy and safety. This study aimed to evaluate the efficacy and safety of alemtuzumab as immune induction therapy in highly sensitized kidney transplant recipients.

METHODSIn this prospective, open-label, randomized, controlled trial, we enrolled 23 highly immunological risk patients (panel reactive antibody > 20%). They were divided into two groups: alemtuzumab group (trial group) and anti-thymocyte globulin (ATG) group (control group). Patients in the alemtuzumab group received intravenous alemtuzumab (15 mg) as a single dose before reperfusion. At the 24th hour post-operation, another dosage of alemtuzumab (15 mg) was given. The control group received a bolus of rabbit ATG (9 mg/kg), which was given 2 hours before kidney transplantation and lasted until the removal of vascular clamps when the anastomoses were completed. Maintenance immunosuppression in both groups comprised standard triple therapy consisting of tacrolimus, prednisone, and mycophenolate mofetil (MMF). Acute rejection (AR) and infection episodes were recorded, and kidney function was monitored during a 2-year follow-up. χ(2) test, t test and Kaplan-Meier analysis were performed with SPSS17.0 software.

RESULTSMedian follow-up was 338 days. In both the alemtuzumab group and ATG group, creatinine and blood urea nitrogen values in surviving recipients were similar (P > 0.05). White blood cell counts were significantly reduced in the alemtuzumab group for the most time points up to 6 months (P < 0.05). One patient receiving alemtuzumab died for acute myocardial infarction at the 65th day post-operation. Two ATG patients died for severe pulmonary infection or cardiac and pulmonary failure. Cumulative 2-year graft survival rate was 90.9% in the alemtuzumab group and 81.8% in ATG group (P > 0.05) respectively. There was one graft failure in the alemtuzumab group and two graft failures in ATG group, with all graft failures at tributed to rejection episodes. The alemtuzumab group had a 2-year cumulative freedom from rejection rate of 81.8%, compared with 72.7% for the ATG group (P > 0.05).

CONCLUSIONAlemtuzumab induction therapy for highly sensitized kidney transplant recipients is an effective and safe protocol yielding an acceptable acute rejection rate.

Adult ; Aged ; Alemtuzumab ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antibodies, Neoplasm ; therapeutic use ; Antilymphocyte Serum ; therapeutic use ; Female ; Graft Rejection ; immunology ; Graft Survival ; immunology ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney Transplantation ; immunology ; Male ; Middle Aged ; Treatment Outcome ; Young Adult

Monoclonal antibodies (mAbs) have become a major class of therapeutic agents providing effective alternatives to treating various human diseases. To date, 15 mAbs have been approved by regulatory agencies in the world for clinical use in oncology indications. The selectivity and specificity, the unique pharmacokinetics, and the ability to engage and activate the host immune system differentiate these biologics from traditional small molecule anticancer drugs. mAb-based regimens have brought clinical benefits, including improvements in overall survival, to patients with a variety of cancers. Many challenges still remain, however, to fully realize the potential of these new medicines. With our further understanding of cancer biology, mechanism of antibody action, and advancement of antibody engineering technologies, many novel antibody formats or antibody-derived molecules are emerging as promising new generation therapeutics. Carefully designed and engineered, they retain the advantage of specificity and selectivity of original antibodies, but in the meantime acquire additional special features such as improved pharmacokinetics, increased selectivity, and enhanced anticancer efficacy. Promising clinical results are being generated with these newly improved antibody-based therapeutics.
Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Antigens, CD20 ; immunology ; Humans ; Immunoconjugates ; therapeutic use ; Neoplasms ; drug therapy ; immunology ; Protein Engineering ; RANK Ligand ; immunology ; Receptor, Epidermal Growth Factor ; immunology ; Receptor, ErbB-2 ; immunology ; Vascular Endothelial Growth Factor A ; immunology

Antibody-based PD-1/PD-L1 blockade therapies have taken center stage in immunotherapies for cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysfunction. In contrast to prior approaches to generate or boost tumor-specific T-cell responses, antibody-based PD-1/PD-L1 blockade targets tumor-induced T-cell defects and restores pre-existing T-cell function to modulate antitumor immunity. In this review, the fundamental knowledge on the expression regulations and inhibitory functions of PD-1 and the present understanding of antibody-based PD-1/PD-L1 blockade therapies are briefly summarized. We then focus on the recent breakthrough work concerning the structural basis of the PD-1/PD-Ls interaction and how therapeutic antibodies, pembrolizumab targeting PD-1 and avelumab targeting PD-L1, compete with the binding of PD-1/PD-L1 to interrupt the PD-1/PD-L1 interaction. We believe that this structural information will benefit the design and improvement of therapeutic antibodies targeting PD-1 signaling.
Antibodies, Monoclonal ; immunology ; therapeutic use ; Antibodies, Monoclonal, Humanized ; immunology ; therapeutic use ; B7-H1 Antigen ; antagonists & inhibitors ; immunology ; Humans ; Neoplasms ; drug therapy ; immunology ; pathology ; Programmed Cell Death 1 Receptor ; antagonists & inhibitors ; immunology ; Signal Transduction ; drug effects ; immunology ; T-Lymphocytes ; immunology

Ulcerative colitis is a chronic inflammatory condition of the colon, characterized by diffuse mucosal inflammation and blood-mixed diarrhea. The main treatment has been 5-aminosalicylic acid, steroid, thiopurine, and anti-tumor necrosis factor alpha (TNF-alpha) antibodies including infliximab, adalimumab, and golimumab. Golimumab, a new anti-TNF-alpha agent has been recently approved for patients with moderate to severe ulcerative colitis. Its efficacy and safety has been demonstrated in line with infliximab and adalimumab in preclinical and clinical studies. This review will focus on golimumab therapy in ulcerative colitis.
Antibodies, Monoclonal/blood/*therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; Clinical Trials as Topic ; Colitis, Ulcerative/*drug therapy ; Drug Administration Schedule ; Humans ; Treatment Outcome ; Tumor Necrosis Factor-alpha/immunology

Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Murine-Derived ; Antigens, CD20 ; immunology ; Antineoplastic Agents ; therapeutic use ; Child, Preschool ; Female ; Humans ; Lymphoma, B-Cell ; drug therapy ; Rituximab ; Treatment Outcome

Epidermal growth factor receptor (EGFR) is mutated, dysregulated or overexpressed in many epithelial malignancies, and EGFR activation has been found to be important in tumor growth and progression. Anti-EGFR monoclonal antibodies target the extracellular domain of EGFR; and show promising anti-tumor potential at clinical trials without severe side effects. In this article the pharmacokenetics and clinical study of 3 anti-EGFR monoclonal antibodies (cetuximab, panitumumab and nimotuzomab) were reviewed.
Antibodies, Monoclonal ; pharmacokinetics ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; therapeutic use ; Cetuximab ; Humans ; Neoplasms ; therapy ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; immunology

OBJECTIVETo evaluate the effectiveness, safety as well as the immunological change (peripheral T cell subpopulation) in patients with idiopathic thrombocytopenic purpura (ITP) treated with lower dose rituximab.

METHODSTwenty-six patients with refractory ITP which were unresponsive to or relapse after steriod and IVIG treatment were treated with rituximab (100 mg per week for four weeks) and intravenous immunoglobulin (IVIG) treatment. Whole blood cell count, serum concentrations of IgG, IgM and IgA, platelet associated (PA)-IgG, PAIgA and PAIgM, peripheral T cell subpopulations, and B cells of CD19(+)/CD20(+) were detected before and after rituximab therapy.

RESULTSComplete response (CR) was achieved in 6 patients (23.1%), response (R) in 10 (38.5%), and non-response (NR) in 10 (38.5%). One patient relapsed after R. The median follow-up time was 5.5 (0.8 - 8) months. The median response and CR time were 27 (1 - 104) and 41 (4 - 109) days, respectively. After the therapy, the serum concentrations of IgG, IgA, IgM, T cells of CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD3(-)CD56(+), CD4(+)CD25(+) and CD4(+)CD25(+)FOXP3(+) were not changed, the number of CD4(+)CD25(+)FOXP3(-) T cells decreased (P < 0.05) and CD19(+)CD20(+) B cells significantly decreased (P < 0.01). PAIgG was lower after treatment compared with that before treatment (P < 0.05). There were no severe adverse effects during rituximab therapy.

CONCLUSIONLower dose rituximab may be an effective and safe modality for patients with ITP.

Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; B-Lymphocytes ; Humans ; Immunoglobulin G ; Purpura, Thrombocytopenic, Idiopathic ; immunology ; Rituximab