Therapeutic Antibodies and Immunologic Conjugates

Dobrenkov, Konstantin; Cheung, Nai‐Kong V.

doi:10.1016/b978-0-323-47674-4.00030-x

Cited by 3 publications

(3 citation statements)

References 337 publications

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“…Immune checkpoints play a key role in the dynamic and balance of the immune system and modulate immune responses in tumor tissues [ 2 , 64 ]. Cancer cells can avoid immune surveillance by targeting immune checkpoints via expressing their inhibitory ligands such as PD-1/PD-L1 axis [ 18 ]. Many of cancer types use the PD-1/PD-L1 pathway, which is associated with inhibitory PD-1 function and PD-L1 overexpression on cancer cells to deactivate T cells [ 65 , 66 ].…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, blocking immune checkpoints such as PD-1 and PD-L1 with mAbs has become a key solution for the reversal of PD-1 pathway-mediated immunosuppression in cancer immunology [ 18 ]. Scientists have found that identifying other immune target agents and combining treatment with other immune checkpoint inhibitors can be effective in achieving a full immune response [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…Owing to the importance of checkpoint inhibitor therapies, in 2018 Tasuku Honjo and James Allison won the Nobel Prize for the discovery of PD-1 and cytotoxic T-lymphocyte antigen-4 (CTLA-4), respectively [ 20 ]. Researchers have also produced mAbs using various laboratory methods, some of them have entered clinical studies that have been successful in the treatment of various tumors and approved by the FDA [ 18 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

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An in silico investigation on the binding site preference of PD-1 and PD-L1 for designing antibodies for targeted cancer therapy

Abdolmaleki,

Ganjalikhani hakemi,

Ganjalikhany

2024

PLoS ONE

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Cancer control and treatment remain a significant challenge in cancer therapy and recently immune checkpoints has considered as a novel treatment strategy to develop anti-cancer drugs. Many cancer types use the immune checkpoints and its ligand, PD-1/PD-L1 pathway, to evade detection and destruction by the immune system, which is associated with altered effector function of PD-1 and PD-L1 overexpression on cancer cells to deactivate T cells. In recent years, mAbs have been employed to block immune checkpoints, therefore normalization of the anti-tumor response has enabled the scientists to develop novel biopharmaceuticals. In vivo affinity maturation of antibodies in targeted therapy has sometimes failed, and current experimental methods cannot accommodate the accurate structural details of protein-protein interactions. Therefore, determining favorable binding sites on the protein surface for modulator design of these interactions is a major challenge. In this study, we used the in silico methods to identify favorable binding sites on the PD-1 and PD-L1 and to optimize mAb variants on a large scale. At first, all the binding areas on PD-1 and PD-L1 have been identified. Then, using the RosettaDesign protocol, thousands of antibodies have been generated for 11 different regions on PD-1 and PD-L1 and then the designs with higher stability, affinity, and shape complementarity were selected. Next, molecular dynamics simulations and MM-PBSA analysis were employed to understand the dynamic, structural features of the complexes and measure the binding affinity of the final designs. Our results suggest that binding sites 1, 3 and 6 on PD-1 and binding sites 9 and 11 on PD-L1 can be regarded as the most appropriate sites for the inhibition of PD-1-PD-L1 interaction by the designed antibodies. This study provides comprehensive information regarding the potential binding epitopes on PD-1 which could be considered as hotspots for designing potential biopharmaceuticals. We also showed that mutations in the CDRs regions will rearrange the interaction pattern between the designed antibodies and targets (PD-1 and PD-L1) with improved affinity to effectively inhibit protein-protein interaction and block the immune checkpoint.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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An in silico investigation on the binding site preference of PD-1 and PD-L1 for designing antibodies for targeted cancer therapy

Abdolmaleki,

Ganjalikhani hakemi,

Ganjalikhany

2024

PLoS ONE

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Radiolabeled Antibodies for Cancer Radioimmunotherapy

Rousseau

Lau

Bénard

2021

Nuclear Medicine and Immunology

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The Diverse Roles of Monoclonal Antibodies in Cancer Immunotherapy and Their Relative Effectiveness: A Literature Review

Ives

Hwang

2022

URNCST Journal

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Introduction: In modern oncology, immunotherapy has emerged as a promising treatment modality for numerous cancers. At the forefront of personalized medicine, immunotherapy utilizes components of a patient's immune system to selectively target cancer cells. Numerous immunotherapy drugs have been developed thus far, including monoclonal antibodies (mAbs). mAbs are genetically identical protein antibodies often isolated and purified from animals through recombinant DNA technology. They are capable of recognizing molecules that are uniquely present on the surface of cancer cells, such as tumour-specific antigens and/or receptors. This narrative review explores the various uses of mAbs in the treatment of cancer. Methods: A narrative literature review was conducted using Pubmed, Medline, and Embase to analyze and synthesize current and prior research surrounding the various uses of mAbs in the context of cancer treatment. Specific examples and potential shortfalls of various treatment methods were also analyzed. Results: mAbs can be used in several distinct ways to target cancerous cells. In the native immunoglobulin G form, mAbs direct immune cells to tumours and induce cytotoxicity by initiating biochemical cascades, leading to effects such as phagocytosis, opsonization, activation of immune cells, degranulation, and cytokine release, among others. mAbs may also be conjugated with radionuclides, or traditional chemotherapeutic agents for targeted drug delivery. They can also be used to target the immune system via conjugation to cytokines or other mAbs which directly interact with immune cells for targeted recruitment. mAbs targeting immune checkpoints can also be used to enhance cancer-related immune responses. However, mAbs are not perfect, and are thus prone to a slew of limitations which are still being addressed. Discussion: mAbs are highly useful, primarily as a result of their specific molecular recognition abilities. This property underlies all uses in cancer immunotherapy and can further be exploited in the development of new immunotherapy technologies and methodologies, along with the elucidation of novel antigens and targets in cancers, to improve the field and address limitations. Conclusion: This literature review aims to synthesize data pertaining to the various potential uses of mAbs in cancer treatment. This approach will provide more insight into the current state of immunotherapeutics, and where additional research must be conducted.

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Therapeutic Antibodies and Immunologic Conjugates

Cited by 3 publications

References 337 publications

An in silico investigation on the binding site preference of PD-1 and PD-L1 for designing antibodies for targeted cancer therapy

An in silico investigation on the binding site preference of PD-1 and PD-L1 for designing antibodies for targeted cancer therapy

Radiolabeled Antibodies for Cancer Radioimmunotherapy

The Diverse Roles of Monoclonal Antibodies in Cancer Immunotherapy and Their Relative Effectiveness: A Literature Review

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