Therapeutic Application Of Monoclonal Antibodies Research Articles

REGULATORY CHALLENGES AND LANDSCAPES OF MONOCLONAL ANTIBODY REGISTRATION: GLOBAL OUTLOOK

Objective: This review aims to illuminate the unprecedented growth and versatile therapeutic landscape of monoclonal antibody (mAb) products, highlighting their significant impact on diverse medical fields such as oncology, septicemia treatment, infection management, and substance abuse disorder interventions. This review outlines the challenges associated with the development, manufacturing, and regulatory approval of monoclonal antibodies, emphasizing the need for diligent attention to overcome these complexities. The review comprehensively examines the historical evolution and therapeutic applications of monoclonal antibodies, emphasizing their potent and versatile characteristics that have enabled successful interventions in challenging regulatory approvals. It delves into the critical considerations in manufacturing, regulatory navigation, and the strategic integration of expedited approval pathways, providing a holistic understanding of the intricate terrain of innovation, clinical translation, and impactful patient care in the realm of monoclonal antibody products. Monoclonal antibodies have significantly advanced medical treatment in various domains, revolutionizing cancer therapy, offering new avenues for septicemia management, augmenting the arsenal against infections, and opening novel pathways for addressing substance abuse disorders. Their development and regulatory approval are associated with challenges of scientific innovation, manufacturing, and regulatory compliance. Despite the challenges, monoclonal antibodies have demonstrated remarkable potential in addressing complex medical conditions. The review serves as a compass, guiding researchers, clinicians, and regulatory authorities through the intricate terrain of monoclonal antibody innovation and clinical translation. It emphasizes the need for diligent attention to overcome the complexities associated with their development and regulatory approval while highlighting their significant impact on advancing patient care.

A Patent Review on the Therapeutic Application of Monoclonal Antibodies in COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains spike proteins that assist the virus in entering host cells. In the absence of a specific intervention, efforts are afoot throughout the world to find an effective treatment for SARS-CoV-2. Through innovative techniques, monoclonal antibodies (MAbs) are being designed and developed to block a particular pathway of SARS-CoV-2 infection. More than 100 patent applications describing the development of MAbs and their application against SARS-CoV-2 have been registered. Most of them target the receptor binding protein so that the interaction between virus and host cell can be prevented. A few monoclonal antibodies are also being patented for the diagnosis of SARS-CoV-2. Some of them, like Regeneron® have already received emergency use authorization. These protein molecules are currently preferred for high-risk patients such as those over 65 years old with compromised immunity and those with metabolic disorders such as obesity. Being highly specific in action, monoclonal antibodies offer one of the most appropriate interventions for both the prevention and treatment of SARS-CoV-2. Technological advancement has helped in producing highly efficacious MAbs. However, these agents are known to induce immunogenic and non-immunogenic reactions. More research and testing are required to establish the suitability of administering MAbs to all patients at risk of developing a severe illness. This patent study is focused on MAbs as a therapeutic option for treating COVID-19, as well as their invention, patenting information, and key characteristics.

Development and validation of a reporter gene assay for bioactivity determination of Anti-CGRP monoclonal antibodies

Calcitonin gene-related peptide (CGRP) is critical for the pathophysiology of migraine, and four therapeutic antibodies targeting CGRP and its corresponding receptors have been approved by the Food and Drug Administration (FDA), while many others are in the different stages of clinical trials. Bioactivity determination is essential for the quality control and clinical application of therapeutic monoclonal antibodies (mAbs). However, no bioassay has been reported to date. In this study, we developed a reporter gene assay (RGA) based on SK-N-MC cells stably expressing firefly luciferase driven by cAMP response element (CRE). The key assay parameters were optimized according to signal-to-noise (SNR), the response value, and the fitted dose-response curve. Validation of the RGA in accordance with ICH-Q2 guidelines showed that the method had good specificity, accuracy, linearity, and precision. The established RGA can be utilized as a reference method for release testing and stability studies of relevant antibodies.

Therapeutic Application of Monoclonal Antibodies in Pancreatic Cancer: Advances, Challenges and Future Opportunities.

Simple SummaryPancreatic cancer is a leading cause of cancer death worldwide. In the majority of patients, cancers are diagnosed at advanced stages of disease and are resistant to current treatments. Therefore, more effective and less toxic therapeutic agents are urgently needed. Monoclonal antibody (mAb)-based technology is an important tool in the discovery of novel therapeutic targets and development of novel therapeutic agents including antibody-based drugs. In this article, we review the therapeutic potential of monoclonal antibody-based agents when used as single agents or in combination with other treatments in pancreatic cancer, factors contributing to the poor response to therapy and emerging opportunities for more effective treatment with antibody-based agents. Pancreatic cancer remains as one of the most aggressive cancer types. In the absence of reliable biomarkers for its early detection and more effective therapeutic interventions, pancreatic cancer is projected to become the second leading cause of cancer death in the Western world in the next decade. Therefore, it is essential to discover novel therapeutic targets and to develop more effective and pancreatic cancer-specific therapeutic agents. To date, 45 monoclonal antibodies (mAbs) have been approved for the treatment of patients with a wide range of cancers; however, none has yet been approved for pancreatic cancer. In this comprehensive review, we discuss the FDA approved anticancer mAb-based drugs, the results of preclinical studies and clinical trials with mAbs in pancreatic cancer and the factors contributing to the poor response to antibody therapy (e.g. tumour heterogeneity, desmoplastic stroma). MAb technology is an excellent tool for studying the complex biology of pancreatic cancer, to discover novel therapeutic targets and to develop various forms of antibody-based therapeutic agents and companion diagnostic tests for the selection of patients who are more likely to benefit from such therapy. These should result in the approval and routine use of antibody-based agents for the treatment of pancreatic cancer patients in the future.

Immunobiology and immunotherapy of HCC: spotlight on innate and innate-like immune cells.

Immune-based therapies such as immune checkpoint inhibitors have revolutionized the systemic treatment of various cancer types. The therapeutic application of monoclonal antibodies targeting inhibitory pathways such as programmed cell death-1(PD-1)/programmed cell death ligand 1 (PD-L1) and CTLA-4 to cells of the adaptive immune system has recently been shown to generate meaningful improvement in the clinical outcome of hepatocellular carcinoma (HCC). Nevertheless, current immunotherapeutic approaches induce durable responses in only a subset of HCC patients. Since immunologic mechanisms such as chronic inflammation due to chronic viral hepatitis or alcoholic and nonalcoholic fatty liver disease play a crucial role in the initiation, development, and progression of HCC, it is important to understand the underlying mechanisms shaping the unique tumor microenvironment of liver cancer. The liver is an immunologic organ with large populations of innate and innate-like immune cells and is exposed to bacterial, viral, and fungal antigens through the gut-liver axis. Here, we summarize and highlight the role of these cells in liver cancer and propose strategies to therapeutically target them. We also discuss current immunotherapeutic strategies in HCC and outline recent advances in our understanding of how the therapeutic potential of these agents might be enhanced.

Therapeutic application of monoclonal antibodies: A review

Therapeutic application of monoclonal antibodies: A review

The pharmacology and therapeutic applications of monoclonal antibodies.

Monoclonal antibodies (mAbs) have emerged as a major class of therapeutic agents on the market. To date, approximately 80 mAbs have been granted marketing approval. In 2018, 12 new mAbs were approved by the FDA, representing 20% of the total number of approved drugs. The majority of mAb therapeutics are for oncological and immunological/infectious diseases, but these are expanding into other disease areas. Over 100 monoclonal antibodies are in development, and their unique features ensure that these will remain a part of the therapeutic pipeline. Thus, the therapeutic value and the elucidation of their pharmacological properties supporting clinical development of these large molecules are unquestioned. However, their utilization as pharmacological tools in academic laboratories has lagged behind their small molecule counterparts. Early therapeutic mAbs targeted soluble cytokines, but now that mAbs also target membrane‐bound receptors and have increased circulating half‐life, their pharmacology is more complex. The principles of pharmacology have enabled the development of high affinity, potent and selective small molecule therapeutics with reduced off‐target effects and drug‐drug interactions. This review will discuss how the same basic principles can be applied to mAbs, with some important differences. Monoclonal antibodies have several benefits, such as fewer off‐target adverse effects, fewer drug‐drug interactions, higher specificity, and potentially increased efficacy through targeted therapy. Modifications to decrease the immunogenicity and increase the efficacy are described, with examples of optimizing their pharmacokinetic properties and enabling oral bioavailability. Increased awareness of these advances may help to increase their use in exploratory research and further understand and characterize their pharmacological properties.

Virulence Determinants Are Required for Brain Abscess Formation Through Staphylococcus aureus Infection and Are Potential Targets of Antivirulence Factor Therapy.

Bacterial brain abscesses (BAs) are difficult to treat with conventional antibiotics. Thus, the development of alternative therapeutic strategies for BAs is of high priority. Identifying the virulence determinants that contribute to BA formation induced by Staphylococcus aureus would improve the effectiveness of interventions for this disease. In this study, RT-qPCR was performed to compare the expression levels of 42 putative virulence determinants of S. aureus strains Newman and XQ during murine BA formation, ear colonization, and bacteremia. The alterations in the expression levels of 23 genes were further confirmed through specific TaqMan RT-qPCR. Eleven S. aureus genes that persistently upregulated expression levels during BA infection were identified, and their functions in BA formation were confirmed through isogenic mutant experiments. Bacterial loads and BA volumes in mice infected with isdA, isdC, lgt, hla, or spa deletion mutants and the hla/spa double mutant strain were lower than those in mice infected with the wild-type Newman strain. The therapeutic application of monoclonal antibodies against Hla and SpA decreased bacterial loads and BA volume in mice infected with Newman. This study provides insights into the virulence determinants that contribute to staphylococcal BA formation and a paradigm for antivirulence factor therapy against S. aureus infections.

Therapeutic Applications of Monoclonal Antibodies in Multiple Sclerosis

Despite the various therapies available, the use of monoclonal antibodies is a highly specific approach that has only recently been of interest to researchers. The properties of antibodies have led to their use in the treatment of various diseases, including cancer, Alzheimer's disease, diabetes and multiple sclerosis (MS). MS, a chronic inflammatory disease, occurs commonly in young adults. The disease is one of the attractive options for monoclonal antibody therapy because it has no definitive drug for its treatment. Antibodies, by targeting different molecules, have different mechanisms to improve the disease. Treatment with monoclonal antibody has culminated in a clear divergence in paradigm and concentration in MS therapeutics. Application of monoclonal antibody in early inflammatory phases can inhibit or postpone the disability in MS subjects. Ocrelizumab and daclizumab are currently under investigation by late phase III trials, and some other monoclonal antibodies are in the early stages of clinical trials. Monoclonal antibodies are of special structural features (including chimeric, humanized, or fully humanized) as well as specific targets (such as stimulation of signal transduction by binding to receptors, blocking interactions, antibody-dependent cell cytotoxicity, complement-dependent cytotoxicity), thus providing various mechanisms of actions during MS therapy. In the present paper, we reviewed different monoclonal antibodies used in MS, their mechanism of action and theirs target molecules.

HYPERTHERMIA AND ITS CLINICAL APPLICATION IN CANCER TREATMENT

The objective of this paper is to describe history of hyperthermia and its clinical applications in cancer treatment. Hyperthermia is a promising approach for cancer therapy which is used to increase the temperature of body tissue by delivering heat obtained from external sources to destroy cancerous cells with minimal or no damaging healthy tissues. There are three main clinical applications of hyperthermia such as local, regional and whole body. Microwaves, radiofrequency, ultrasound, infrared and different kinds of hot sources (hot water, ferromagnetic, nanoparticles) heating approaches are used in some clinical trials. Hyperthermia is administered as an adjuvant to other cancer treatment modalities (multimodal oncological strategies). However, hyperthermia is still facing many challenges in cancer treatment. Some trials continue to use hyperthermia in combination with other novel interstitial technologies such as magnetic fluid hyperthermia and thermolabile liposomes, application of therapeutic monoclonal antibodies under hyperthermic conditions, and hyperthermia- induced gene therapy for the treatment of different cancers which have been discussed. Thus, progress of hyperthermia in clinical applications has already shown some benefits to cancer patients.

Studies on the influence of different designs of eukaryotic vectors on the expression of recombinant IgA

Production and application of therapeutic monoclonal antibodies are second only to vaccines in the world pharmaceutical market. The most common therapeutic antibodies are monoclonal antibodies (mAbs) of the IgG isotype that are produced in eukaryotic CHO cells. In recent years, there has been a considerable interest in developing treatment medications based on IgA antibodies, which can have a wide range of effector functions on human mucous membranes. To study the expression level of immunoglobulin A (IgA) in mammal cells, we designed a set of bipromoter (CMV and EF1α) vectors. The vectors contain gene fragments that encode the heavy chain variable domain (VH) and the light chain variable domain (VL) of the human monoclonal antibody FI6v3 against the hemagglutinin of influenza virus A. They also contain gene fragments that encode the light chain (kappa type) constant domain and the heavy chain constant domain of the human antibody IgA1. The expression vectors differed in the orientation of the promoters and the presence or absence of introns. Two variants of the full-length light and heavy chains were cloned into a eukaryotic expression vector in head-to-head and head-to-tail orientations. The resulting plasmids were transfected into CHO-DG44 and HEK-293T cells. The antibody expression level for the stable transfection of CHO-DG44 and HEK-293T cell cultures was determined by ELISA. The results of the experiments showed that the expression of FI6v3-IgA1 antibodies significantly increased when eukaryotic cells were transfected with the plasmid pBiPr-ABIgA1FI6-Iht in which the heavy chain of IgA1 contains introns and the promoters are arranged head-to-tail.

Therapeutic Application of Monoclonal Antibodies in Multiple Sclerosis.

Multiple sclerosis (MS) is a heterogeneous inflammatory demyelinating disorder of the central nervous system (CNS). People with MS typically have a relapsing remitting disease course, with episodic neurological dysfunction corresponding to inflammation in the brain or spinal cord. Some relapsing patients develop a secondary progressive disease course, with accumulation of disability over time, yet other people with MS only experience a primary progressive course. Over the past 20 years, 14 immunomodulatory therapies have been approved in MS in order to reduce the frequency of inflammatory relapses and prevent CNS damage. Of the available types of therapies, the monoclonal antibodies are generally the most effective at dampening MS disease activity. In this review we will discuss the development of effective monoclonal antibody therapies coinciding with a better understanding of the complex immunopathogenesis of MS, both successes and failures, as well as targets for future development that address the mechanisms underlying progressive disease.

<sup>89</sup>Zr-PET Radiochemistry in the Development and Application of Therapeutic Monoclonal Antibodies and Other Biologicals

Positron emission tomography with (89)Zr can be used to follow the behaviour of therapeutic monoclonal antibodies (mAbs) and other biologicals in vivo. The favourable radiophysical characteristics of (89)Zr allow multiple days PET scanning after injection. For the coupling of (89)Zr to proteins six desferrioxamine (DFO)-based bifunctional chelators have been described, five of which forming stable complexes in vivo. Of the methods that give stable complexes three are based on random lysine modification of mAbs and two on site-specific engineering. Up to now only two methods, random lysine modification with N-suc-DFO or DFO-Bz-NCS, have been used in clinical studies. In this review firstly aspects of the physicochemical properties and production of (89)Zr are emphasized as well as important items that have to be taken into account for current good manufacturing practice (cGMP) compliant production of (89)Zr-labeled proteins. Next, the different DFO-based conjugation strategies will be discussed with respect to synthesis, and their (pre)clinical evaluation particularly in the field of oncology.

Characteristics of anaphylaxis‐inducing IgG immune complexes triggering murine passive systemic anaphylaxis

With the broad and increasing application of therapeutic monoclonal antibodies (mAbs) in clinical settings, IgG-induced allergic reactions, including passive systemic anaphylaxis (PSA), have attracted significant attention. However, it is not clear which types of IgG mAb-antigen complexes or IgG aggregates formed by antigen binding can trigger PSA, as not all immune complexes (ICs) are capable of triggering PSA. Here, we characterise mAb-antigen complexes capable of inducing murine PSA to evaluate and predict which ICs are able to induce PSA. Thirty-six combinatory reactions with eight antigens and 27 corresponding mAbs were used to trigger PSA, which was defined by rectal temperature. Sandwich ELISA, passive cutaneous anaphylaxis (PCA) induction and flow cytometry analysis of CD16/32 (FcγRIII/II) expression were used to characterise the ICs. The dynamic concentrations of antigen in the peripheral blood were measured by ELISA. Only 14 of the 36 ICs could trigger PSA and thus be termed anaphylaxis-inducing immune complexes (Ai-ICs). The Ai-ICs could be characterised by constructing sandwich ELISA, inducing PCA and down-regulating CD16/32 (FcγRIII/II) expression on blood neutrophils in vitro and in vivo. Additionally, the occurrence and severity of PSA was found to be associated with the instantaneous concentration of antigen in the peripheral blood in the presence of antibody. Only Ai-ICs, not all ICs, could trigger IgG-mediated PSA, which could be characterised by the above simple methods. The occurrence and severity of PSA was associated with the instantaneous concentration of antigen in the peripheral blood in the presence of antibody.

Therapeutic application of monoclonal antibodies in cancer: advances and challenges

Monoclonal antibody (mAb)-based products are highly specific for a particular antigen. This characteristic feature of the molecules makes them an ideal tool for many applications including cancer diagnosis and therapy. We performed comprehensive searches of PubMed, Medline and the Food and Drug Administration website using keywords such as 'therapeutic antibodies' and 'anti-cancer antibodies'. Treatment of cancer patients with antibodies when used alone or in combination with chemotherapy and radiotherapy, or conjugated to drugs or radioisotopes, prolongs overall survival in cancer patients. Currently, there are 14 mAb-based drugs that have been approved for the treatment of cancer patients. The response of cancer patients to antibody therapy can be of short duration. Therapeutic antibodies are expensive and may have side effects. There are no reliable predictive biomarkers for sensitivity or resistance to certain therapeutic antibodies. FUTURE FOCUS: There should be additional studies to discover novel therapeutic targets, to develop more effective antibody-based drugs with fewer side effects, to identify more reliable predictive biomarker(s) for response to therapy with antibody-based drugs and to develop alternative strategies (e.g. transgenic plants, transgenic farm animals) for production of large quantities and more affordable batches of therapeutic antibodies. A better understanding of cancer biology, the hallmarks of human cancers and the immune system would lead to identification of additional cell surface biomarkers. These in turn would facilitate the development of novel and biosimilar antibody-based drugs and their routine use as 'magic bullets' for the targeted therapy of human cancers.

Correlation of ADCC activity with cytokine release induced by the stably expressed, glyco-engineered humanized Lewis Y-specific monoclonal antibody MB314

A major limitation to the application of therapeutic monoclonal antibodies (mAbs) is their reduced in vivo efficacy compared with the high efficacy measured in vitro. Effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) are dramatically reduced in vivo by the presence of high amounts of endogenous IgG in the serum. Recent studies have shown that modification of the glycosylation moieties attached to the Fc part of the mAb can enhance binding affinity to FcγRIIIα receptors on natural killer cells and thus may counteract the reduced in vivo efficacy. In the present study, a humanized IgG1/κ monoclonal antibody recognizing the tumor-associated carbohydrate antigen Lewis Y was stably produced in a moss expression system that allows glyco-engineering. The glyco-modified mAb (designated MB314) showed a highly homogeneous N-glycosylation pattern lacking core-fucose. A side-by-side comparison to its parental counterpart produced in conventional mammalian cell-culture (MB311, formerly known as IGN311) by fluorescence-activated cell sorting analysis confirmed that the target specificity of MB314 is similar to that of MB311. In contrast, ADCC effector function of MB314 was increased up to 40-fold whereas complement dependent cytotoxicity activity was decreased 5-fold. Notably, a release of immunostimulatory cytokines, including interferon γ, monocyte chemotactic protein-1 (MCP-1), interleukin-6 and tumor necrosis factor (TNF) was particularly induced with the glyco-modified antibody. TNF release was associated with CD14+ cells, indicating activation of monocytes.

Therapeutic application of monoclonal antibodies in multiple sclerosis: focus on alemtuzumab

Therapeutic application of monoclonal antibodies in multiple sclerosis: focus on alemtuzumab Masaaki NiinoDepartment of Clinical Research, Hokkaido Medical Center, Sapporo, JapanAbstract: Recent progress in the treatment of multiple sclerosis (MS) is significant, and the potential of monoclonal antibodies (mAbs) for the treatment of MS has been highlighted. Natalizumab demonstrated a high level of efficacy for MS and is the first mAb to be approved for treatment of MS. Clinical trials of several types of mAbs for treatment of MS are in progress, and mAbs are expected to become the new choice of treatment for MS. Alemtuzumab is one of the most promising mAbs for treatment for MS, despite some side effects to be considered such as autoimmune hyperthyroidism, Goodpasture’s syndrome, and autoimmune idiopathic thrombocytopenic purpura. Any therapeutic agents for MS may carry risks of short- or long-term side effects; however, information regarding the long-term side effects of these new agents is lacking. Long-term adverse effects can often be recognized after the approval of agents. Here, recent progress on mAbs for the treatment of MS is reviewed, with a focus on alemtuzumab.Keywords: multiple sclerosis, monoclonal antibody, alemtuzumab, therapy, experimental autoimmune encephalomyelitis

Therapeutic applications of monoclonal antibodies

Monoclonal antibodies drive the development of multibillion dollar biotechnology industry. Many of the pharmaceuticals companies have entered monoclonal antibodies sector, attracted by quicker and less costly development, higher success rates, premium pricing, and potentially reduced threats from generics. The ideal treatment of rheumatoid arthritis (RA) should be safe, produce sustained disease remission and stop radiological damage after a brief course of treatment. If repeated treatments are necessary, they must be safe and economical to use in the long term. It is against these criteria that new treatments for RA, including mAb, should and will be assessed. Monoclonal antibodies are used in the treatment of cancer, including leukemia, colorectal cancer, breast cancer and non-Hodgkin’s lymphoma, RA, ischemic heart disease and transplant rejection. How to Cite this Article Pubmed Style Prajapati DS, Shah JS, Dave JB, Patel CN. Applications of Monoclonal SRP. 2011; 2(1): 37-42. doi:10.4103/0975-8453.83437 Web Style Prajapati DS, Shah JS, Dave JB, Patel CN. Applications of Monoclonal http://www.sysrevpharm.org/?mno=302644609 [Access: March 28, 2021]. doi:10.4103/0975-8453.83437 AMA (American Medical Association) Style Prajapati DS, Shah JS, Dave JB, Patel CN. Applications of Monoclonal SRP. 2011; 2(1): 37-42. doi:10.4103/0975-8453.83437 Vancouver/ICMJE Style Prajapati DS, Shah JS, Dave JB, Patel CN. Applications of Monoclonal SRP. (2011), [cited March 28, 2021]; 2(1): 37-42. doi:10.4103/0975-8453.83437 Harvard Style Prajapati DS, Shah JS, Dave JB, Patel CN (2011) Applications of Monoclonal SRP, 2 (1), 37-42. doi:10.4103/0975-8453.83437 Turabian Style Prajapati DS, Shah JS, Dave JB, Patel CN. 2011. Applications of Monoclonal Systematic Reviews in Pharmacy, 2 (1), 37-42. doi:10.4103/0975-8453.83437 Chicago Style Prajapati DS, Shah JS, Dave JB, Patel CN. Therapeutic Applications of Monoclonal Antibodies. Systematic Reviews in Pharmacy 2 (2011), 37-42. doi:10.4103/0975-8453.83437 MLA (The Modern Language Association) Style Prajapati DS, Shah JS, Dave JB, Patel CN. Therapeutic Applications of Monoclonal Antibodies. Systematic Reviews in Pharmacy 2.1 (2011), 37-42. Print. doi:10.4103/0975-8453.83437 APA (American Psychological Association) Style Prajapati DS, Shah JS, Dave JB, Patel CN (2011) Applications of Monoclonal Systematic Reviews in Pharmacy, 2 (1), 37-42. doi:10.4103/0975-8453.83437

Biodistribution Mechanisms of Therapeutic Monoclonal Antibodies in Health and Disease

The monoclonal antibody market continues to witness an impressive rate of growth and has become the leading source of expansion in the biologic segment within the pharmaceutical industry. Currently marketed monoclonal antibodies target a diverse array of antigens. These antigens are distributed in a variety of tissues such as tumors, lungs, synovial fluid, psoriatic plaques, and lymph nodes. As the concentration of drug at the proximity of the biological receptor determines the magnitude of the observed pharmacological responses, a significant consideration in effective therapeutic application of monoclonal antibodies is a thorough understanding of the processes that regulate antibody biodistribution. Monoclonal antibody distribution is affected by factors such as molecular weight, blood flow, tissue and tumor heterogeneity, structure and porosity, target antigen density, turnover rate, and the target antigen expression profile.

Monoclonal antibody therapy for central nervous system lymphomas: an emerging treatment paradigm

The management of CNS lymphomas is poised for another revolution due to the emergence of therapeutic monoclonal antibodies. As the technology for generating monoclonal antibodies matures and obstacles are solved, therapeutic monoclonal antibodies will play an increasing role in the management of cancer. This article will review the biology of CNS lymphomas, monoclonal antibody technology, limitation of existing chemotherapies and the application of therapeutic monoclonal antibodies for the treatment of CNS lymphomas.