Bispecific Antibodies For T Cell Based Immunotherapy
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Bispecific Antibodies For T Cell Based Immunotherapy
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Author : Brian H. Santich
language : en
Publisher: Frontiers Media SA
Release Date : 2021-01-21
Bispecific Antibodies For T Cell Based Immunotherapy written by Brian H. Santich and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021-01-21 with Medical categories.
CK is affiliated with the Roche Innovation Center Zurich, holds stocks and has patents with Hoffmann-La Roche company. NKC reports receiving commercial research grants from Y-mabs Therapeutics and Abpro-Labs Inc.; holding ownership interest/equity/options in Y-Mabs Therapeutics Inc., and in Abpro-Labs, and owning stock options in Eureka Therapeutics. NKC is the inventor of pending and issued patents filed by MSK, including hu3F8 and 8H9 licensed to Ymabs Therapeutics, beta-glucan to Biotec Pharmacon, and HER2 bispecific antibody to Abpro-labs. NKC is an advisory board member for Abpro-Labs and Eureka Therapeutics
Bispecific Antibodies
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Author : Roland E. Kontermann
language : en
Publisher: Springer Science & Business Media
Release Date : 2011-07-21
Bispecific Antibodies written by Roland E. Kontermann and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011-07-21 with Medical categories.
The concept of using bispecific antibodies for cancer therapy by retargeting immune effector cells was developed several years ago. Initial clinical studies were rather disappointing mainly due to low efficacy, severe side effects and the immunogenicity of the bispecific antibodies. The progress in antibody engineering finally led to the generation of new classes of bispecific antibodies lacking these obstacles. In addition, new applications were established, such as pre-targeting strategies in radioimmunotherapy and dual targeting approaches in order to improve binding, selectivity and efficacy. In this book, the different ways of generating bispecific antibodies are described, with emphasis on recombinant formats. The various applications of bispecific antibodies, e.g. in cellular cancer immunotherapy, radioimmunotherapy and pretargeting strategies are covered, and emerging applications such as dual targeting strategies, which involve the simultaneous inhibition of two targets, are addressed.
Nanoparticle T Cell Engagers As A Modular Platform For Cancer Immunotherapy
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Author : Kinan Alhallak
language : en
Publisher:
Release Date : 2021
Nanoparticle T Cell Engagers As A Modular Platform For Cancer Immunotherapy written by Kinan Alhallak and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021 with categories.
Immunotherapy has advanced significantly in recent years due to its promising clinical outcomes in a variety of malignancies and holds great promise in becoming the "cure" for cancer. Cancer immunotherapy is the treatment that stimulates a person's own immune system to recognize, target, and eliminate cancer cells. As the field progresses with emerging and novel strategies, the ability to manipulate the immune system while mitigating toxicities is the goal for clinical translation. To control for both efficacy and safety, biomaterials have been incorporated into immunotherapies to achieve tissue- and/or cell-specific immunomodulation, overcome immunosuppression, and address tumor microenvironment heterogeneity.T cell-based immunotherapy, such as chimeric antigen receptor (CAR)-T cells, has shown promising clinical outcomes in many cancers. CAR-T cells are autologous T cells that have been virally transfected to express an engineered CAR construct, containing a synthesized fragment that targets the desired surface antigen on the target cell. However, this therapy has significant limitations such as toxicity, the long-term safety profile of the viral vector, the need to perform quality control testing frequently throughout the production of CAR-T cells, the high costs associated with extensive labor and expensive facility equipment, complex production, and the inability to target multiple tumor antigens with one CAR-T cell. In addition to CAR-T cells, T cell-based therapy can be pursued with T cell engagers (TCEs). TCEs consists of two single chain variable fragments which are connected by a protein linker. One of the domains recognizes a tumor-associated surface antigen, while the other recognizes the T cell using the CD3 receptor. TCEs demonstrate high potency and efficacy against tumor cells and exploit the use of endogenous T cells, circumventing the limitation of genetically engineering extracted patient T cells to express CARs. The disadvantages of TCEs, however, include toxicity, laborious and tedious production, short pharmacokinetics (PK), and the inability to target multiple cancer surface markers Moreover, both CART and TCE therapies confer the development of antigen-less clones, causing tumor escape and relapse in multi-clonal diseases; and inability to induce T cell persistent activation, ultimately causing T cell exhaustion. We developed nanoparticle-based bispecific T cell engagers (nanoBTCEs), which are liposomes decorated with anti-CD3 monoclonal antibodies targeting T cells, and monoclonal antibodies targeting one cancer antigen. NanoBTCEs 1) have a long half-life of about 60 hours, which enables once-a-week administration instead of continuous infusion; 2) induce T cell activation in the presence of Waldenstrom Macroglobulinemia (WM) and multiple myeloma (MM) cells; and 3) induce T cell-mediated cancer cell lysis of WM and MM cells. Due to the nanoparticulate nature of nanoBTCEs, we solved the PK problem, enabled simple and cheap production, and created an off-the-shelf platform for cancer immunotherapy. For multi-clonal diseases such as MM, we also developed nanoparticle-based multispecific T cell engagers (nanoMuTEs), which are liposomes decorated with anti-CD3 monoclonal antibodies targeting T cells, and monoclonal antibodies targeting more than one cancer antigen. NanoMuTEs targeting multiple cancer antigens showed greater efficacy in MM cells in vitro and in vivo, compared to nanoBTCEs targeting only one cancer antigen. Unlike nanoBTCEs, treatment with nanoMuTEs didn't cause downregulation (or loss) of a single antigen and prevented the development of antigen-less tumor escape. Our nanoparticle-based immuno-engaging technology provides a solution for the major limitations of current immunotherapy technologies. In addition, a major disadvantage TCEs have is that their T cell activation and persistence is weaker than CAR-T cells, which is why CAR-T cells have a greater anti-tumor response compared to TCEs. Methods to activate T cells include the use of lectins, such as phytohemagglutinin (PHA) which is commonly only used for research purposes ex vivo, but not in vivo. PHA binds to glycoproteins on the T cell receptor and stimulates T cells more significantly compared to other forms of T cell activators such as phorbol 12-myristate 13- acetate, ionomycin, and concanavalin A. Yet, PHA has not been used to activate T cells in vivo, for immunotherapy, due to its biological instability and toxicity. The instability stems from its protein-nature, which causes its degradation and short bioavailability profile in the blood while toxicity can cause death due to agglutination of red and white blood cells. Therefore, to take full advantage of PHA as an immune activator, an approach of circumventing the limitations of PHA while also preserving function is needed. We report the encapsulation of PHA in a liposome which increased the in vivo stability, reduce toxicity, and activated T cells in vitro and in vivo, and induced killing of tumor cells in vitro and in vivo. The liposomal PHA is a new form of pan- cancer immunotherapy which acts regardless of tumor antigens and thus does not induce antigen- less tumor escape while also circumventing current obstacles of T cell exhaustion. In conclusion, our nanoTCE platform uses nanoparticles to create a relatively simple, reproducible, and off-the-shelf solution to overcome the major limitations of current immunotherapy techniques such as TCEs and CAR-T cells. The nanoTCE targets each antigen with the high specificity of monoclonal antibodies which enables the creation of a more robust immunotherapy technology to take advantage of the immune system for an effective response. Our system enables the customization of the nanoTCE as an immunotherapy with the use of existing monoclonal antibodies for the targeting of any desired cancer or immune cell antigen. This simple, customizable, specific, translational, and efficacious nanoTCE platform provides the flexibility to engage any immune cell for the treatment of the cancer of interest and can be used for personalized medicine based on the cancer antigens presented by the patient's tumor.
Current Immunotherapeutic Strategies In Cancer
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Author : Matthias Theobald
language : en
Publisher: Springer Nature
Release Date : 2019-08-31
Current Immunotherapeutic Strategies In Cancer written by Matthias Theobald and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-08-31 with Medical categories.
This book offers a comprehensive review of recent advances in cancer immunotherapy, and explores the value and limitations of the most effective current therapeutic strategies and emerging treatment modalities. It discusses in detail the successes achieved using monoclonal antibodies (mAbs), including developments with regard to conjugated mAbs and also bispecific mAbs as novel treatment options for leukemia and solid tumors. It also examines the advances toward personalized immunotherapy, focusing on the effectiveness of adoptive cell therapy using genetically engineered T cells with tumor-associated antigen-specific T-cell receptors and chimeric antigen receptors, as well as the role of tailored vaccines based on the patient’s cancer mutanome. Further, it describes the impressive therapeutic results recently achieved with checkpoint inhibitors, and analyzes novel strategies to modulate the immunosuppressive tumor microenvironment. Written by leading international experts and providing up-to-date information on emerging strategies, such as oncolytic virus-based therapy, epigenetic therapy, and combination therapy, the book appeals to all those with an interest in immunotherapy as it comes of age.
Nanobody Based Cancer Immunotherapy And Immunoimaging
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Author : Zahra Sharifzadeh
language : en
Publisher: Frontiers Media SA
Release Date : 2023-06-07
Nanobody Based Cancer Immunotherapy And Immunoimaging written by Zahra Sharifzadeh and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2023-06-07 with Science categories.
Biomaterials For Cancer Therapeutics
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Author : Kinam Park
language : en
Publisher: Elsevier
Release Date : 2013-11-23
Biomaterials For Cancer Therapeutics written by Kinam Park and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013-11-23 with Technology & Engineering categories.
Cancer can affect people of all ages, and approximately one in three people are estimated to be diagnosed with cancer during their lifetime. Extensive research is being undertaken by many different institutions to explore potential new therapeutics, and biomaterials technology is now being developed to target, treat and prevent cancer. This unique book discusses the role and potential of biomaterials in treating this prevalent disease.The first part of the book discusses the fundamentals of biomaterials for cancer therapeutics. Chapters in part two discuss synthetic vaccines, proteins and polymers for cancer therapeutics. Part three focusses on theranosis and drug delivery systems, whilst the final set of chapters look at biomaterial therapies and cancer cell interaction.This extensive book provides a complete overview of the latest research into the potential of biomaterials for the diagnosis, therapy and prevention of cancer. Biomaterials for cancer therapeutics is an essential text for academics, scientists and researchers within the biomedical industry, and will also be of interest to clinicians with a research interest in cancer therapies and biomaterials. A complete overview of the latest research into the potential of biomaterials for the diagnosis, therapy and prevention of cancer Discusses the fundamentals of biomaterials for cancer therapeutics Discusses synthetic vaccines, proteins and polymers for cancer therapeutics
Successful Drug Discovery Volume 3
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Author : J¿nos Fischer
language : en
Publisher: John Wiley & Sons
Release Date : 2018-06-05
Successful Drug Discovery Volume 3 written by J¿nos Fischer and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-06-05 with Medical categories.
With its focus on drugs so recently introduced that they have yet to be found in any other textbooks or general references, the information and insight found here makes this a genuinely unique handbook and reference. Following the successful approach of the previous volumes in the series, inventors and primary developers of successful drugs from both industry and academia tell the story of the drug's discovery and describe the sometimes twisted route from the first drug candidate molecule to the final marketed drug. The 11 case studies selected describe recent drugs ranging across many therapeutic fields and provide a representative cross-section of present-day drug developments. Backed by plenty of data and chemical information, the insight and experience of today's top drug creators makes this one of the most useful training manuals that a junior medicinal chemist may hope to find. The International Union of Pure and Applied Chemistry has endorsed and sponsored this project because of its high educational merit.
Progress In Clinical And Biological Research
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Author : George J. Brewer
language : en
Publisher:
Release Date : 1975
Progress In Clinical And Biological Research written by George J. Brewer and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1975 with Biology categories.
Resistance To Targeted Therapies In Lymphomas
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Author : Ana C. Xavier
language : en
Publisher: Springer
Release Date : 2020-09-30
Resistance To Targeted Therapies In Lymphomas written by Ana C. Xavier and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-09-30 with Medical categories.
Over the past few decades, lymphoma patient outcomes have improved as a result of multidrug chemotherapy and radiation therapy, intensification of treatment, improvement in supportive care, and better imaging and staging systems. Even more recently, there has been tremendous progress in the understanding of cancer cell biology and its microenvironment which has resulted in the development of biologic agents, also called "target" therapies. These therapies are more specific in targeting cancer cells either directly or via enhancement of the immune system. Many clinical studies have focused on biological agents in combination with traditional chemotherapy with the goal of improved outcomes, or reduced acute long term complications that are associated with lymphoma therapy. This volume will review different classes of "target" drugs that have been developed, approved, or are under investigation in the field of lymphoma therapy. The discussion will not only be on the understanding of the mechanisms of action or clinical response of those agents, but will also help the reader to understand the nature of lymphoma biology in patients who relapse or are refractor after exposure to those drugs. Contributors will discuss what is currently known about mechanisms of tumor-related or host-related resistance, and how to overcome this resistance. This understanding is crucial given the dismal outcomes of patients with relapsed or refractory lymphomas. The book provides a unique opportunity to review and reflect on the recent successes and pitfalls of the modern lymphoma therapy era.
Cancer Vaccines And Immunotherapy
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Author : Peter L. Stern
language : en
Publisher: Cambridge University Press
Release Date : 2000-08-17
Cancer Vaccines And Immunotherapy written by Peter L. Stern and has been published by Cambridge University Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2000-08-17 with Medical categories.
Rapid progress in the definition of tumor antigens, and improved immunization methods, bring effective cancer vaccines within reach. In this wide-ranging survey, leading clinicians and scientists review therapeutic cancer vaccine strategies against a variety of diseases and molecular targets. Intended for an interdisciplinary readership, their contributions cover the rationale, development, and implementation of vaccines in human cancer treatment, with specific reference to cancer of the cervix, breast, colon, bladder, and prostate, and to melanoma and lymphoma. They review target identification, delivery vectors and clinical trial design. The book begins and ends with lucid overviews from the editors, that discuss the most recent developments.