Bispecific anti-PD-1/LAG-3 antibodies for treatment of advanced or metastatic solid tumors: a patent evaluation of US2018326054

ABSTRACT

Introduction

Due to the primary role of PD-1 and LAG-3 in regulating the immune response in tumors, there is a need to develop therapies focused on the inhibition of PD-1 and LAG-3 in order to improve the immune response in patients with cancer. The authors of US2018326054 patent propose a method to eradicate cancer by using bispecific anti-PD-1/LAG-3 antibodies.

Areas covered

The US2018326054 patent describes anti-PD-1/LAG3 antibodies, pharmaceutical composition that contains it, and their application for cancer treatment, particularly pancreatic carcinoma. Proof concept and preclinical results show anti-PD-1/LAG-3 bispecific antibodies bind and are internalized by CD4 + T cells thereby increasing their effector functions (release of Granzyme B and INF-γ) in the presence of tumor cells, and completely suppress tumors in a murine model.

Expert opinion

Anti-PD-1/LAG-3 bispecific antibodies of the US2018326054 patent are new in a general concept, but treatment data is only shown for pancreatic carcinoma. The results to be obtained in future clinical trials of safety and efficacy could conclude whether these bispecific anti-PD-1/LAG-3 antibodies will be useful in a cancer treatment scheme.

KEYWORDS:

• PD-1
• LAG-3
• cancer
• immunotherapy
• bispecific
• antibody

Article highlights

• The bispecific anti-PD-1/LAG-3 antibodies described in patent US2018326054 are new compared to the state of the art.

• The bispecific antibodies have a KD of 1.8 nM for PD-1 and a KD of 2.82 nM and 4.63 nM for LAG-3.

• The bispecific antibodies increase the effector functions of tumor antigen-specific T cells.

• The bispecific antibodies cause a secretion of Granzyme B by CD4+ T cells in co-culture with lymphoblastoid B cell line.

• Treatment with bispecific antibody 8311 of humanized NSG mice inoculated with pancreatic carcinoma cells suppresses the tumor.

Acknowledgments

We thank the Mexican people for the support, through their taxes, provided for the development of this article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they are a co-inventor. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.