The FG Loop of PD-1 Serves as a “Hotspot” for Therapeutic Monoclonal Antibodies in Tumor Immune Checkpoint Therapy

AbstractAnti-CTLA-4 and anti-PD-1/PD-L1 immune checkpoint inhibitors are therapeutic monoclonal antibodies that do not target cancer cells but are designed to reactivate or promote antitumor immunity. Dosing and scheduling of these biologics were established according to conventional drug development models, even though the determination of a maximum tolerated dose in the clinic could only be defined for anti-CTLA-4. Given the pharmacology of these monoclonal antibodies, their high interpatient pharmacokinetic variability, the actual clinical benefit as monotherapy that is observed only in a specific subset of patients, and the substantial cost of these treatments, a number of questions arise regarding the selected dose and the dosing interval. This review aims to outline the development of these immunotherapies and considers optimization options that could be used in clinical practice.

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Therapeutic Monoclonal Antibodies Targeting Immune Checkpoints for the Treatment of Solid Tumors

Antibodies ◽

10.3390/antib8040051 ◽

2019 ◽

Vol 8 (4) ◽

pp. 51 ◽

Cited By ~ 6

Author(s):

Gravbrot ◽

Gilbert-Gard ◽

Mehta ◽

Ghotmi ◽

Banerjee ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Immune Checkpoint ◽

Side Effect ◽

Chemotherapeutic Agents ◽

Immune Checkpoints ◽

Side Effect Profile ◽

Durable Response ◽

Solid Malignancies ◽

Therapeutic Monoclonal Antibodies ◽

Review Current

Recently, modulation of immune checkpoints has risen to prominence as a means to treat a number of solid malignancies, given the durable response seen in many patients and improved side effect profile compared to conventional chemotherapeutic agents. Several classes of immune checkpoint modulators have been developed. Here, we review current monoclonal antibodies directed against immune checkpoints that are employed in practice today. We discuss the history, mechanism, indications, and clinical data for each class of therapies. Furthermore, we review the challenges to durable tumor responses that are seen in some patients and discuss possible interventions to circumvent these barriers.

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Design of Innovative Therapeutic Monoclonal Antibodies

Biotekhnologiya ◽

10.21519/0234-2758-2017-33-1-10-29 ◽

2017 ◽

pp. 10-29

Author(s):

A.V. Karabelskii ◽

◽

T.A. Nemankin ◽

A.B. Ulitin ◽

A.S. Vaganov ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Therapeutic Monoclonal Antibodies

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Therapeutic Monoclonal Antibodies in Clinical Practice against Cancer

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200703191653 ◽

2020 ◽

Vol 20 (16) ◽

pp. 1895-1907

Author(s):

Navgeet Kaur ◽

Anju Goyal ◽

Rakesh K. Sindhu

Keyword(s):

Monoclonal Antibody ◽

Monoclonal Antibodies ◽

Clinical Practice ◽

Therapeutic Agent ◽

Hematologic Malignancies ◽

Immune Checkpoints ◽

Malignant Cells ◽

Main Target ◽

Therapeutic Monoclonal Antibodies ◽

Cancerous Cells

The importance of monoclonal antibodies in oncology has increased drastically following the discovery of Milstein and Kohler. Since the first approval of the monoclonal antibody, i.e. Rituximab in 1997 by the FDA, there was a decline in further applications but this number has significantly increased over the last three decades for various therapeutic applications due to the lesser side effects in comparison to the traditional chemotherapy methods. Presently, numerous monoclonal antibodies have been approved and many are in queue for approval as a strong therapeutic agent for treating hematologic malignancies and solid tumors. The main target checkpoints for the monoclonal antibodies against cancer cells include EGFR, VEGF, CD and tyrosine kinase which are overexpressed in malignant cells. Other immune checkpoints like CTLA-4, PD-1 and PD-1 receptors targeted by the recently developed antibodies increase the capability of the immune system in destroying the cancerous cells. Here, in this review, the mechanism of action, uses and target points of the approved mAbs against cancer have been summarized.

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COVID-19: Unmasking Emerging SARS-CoV-2 Variants, Vaccines and Therapeutic Strategies

Biomolecules ◽

10.3390/biom11070993 ◽

2021 ◽

Vol 11 (7) ◽

pp. 993

Author(s):

Renuka Raman ◽

Krishna J. Patel ◽

Kishu Ranjan

Keyword(s):

Immune Response ◽

Monoclonal Antibodies ◽

Severe Acute Respiratory Syndrome ◽

Small Molecules ◽

Viral Vector ◽

Therapeutic Strategies ◽

Convincing Evidence ◽

Plasma Therapy ◽

Therapeutic Monoclonal Antibodies ◽

Increased Susceptibility

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, which has been a topic of major concern for global human health. The challenge to restrain the COVID-19 pandemic is further compounded by the emergence of several SARS-CoV-2 variants viz. B.1.1.7 (Alpha), B.1.351 (Beta), P1 (Gamma) and B.1.617.2 (Delta), which show increased transmissibility and resistance towards vaccines and therapies. Importantly, there is convincing evidence of increased susceptibility to SARS-CoV-2 infection among individuals with dysregulated immune response and comorbidities. Herein, we provide a comprehensive perspective regarding vulnerability of SARS-CoV-2 infection in patients with underlying medical comorbidities. We discuss ongoing vaccine (mRNA, protein-based, viral vector-based, etc.) and therapeutic (monoclonal antibodies, small molecules, plasma therapy, etc.) modalities designed to curb the COVID-19 pandemic. We also discuss in detail, the challenges posed by different SARS-CoV-2 variants of concern (VOC) identified across the globe and their effects on therapeutic and prophylactic interventions.

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