COM701, A FIRST-IN-CLASS IMMUNE CHECKPOINT INHIBITOR, TARGETS A NOVEL TUMOR PROMOTING PATHWAY MEDIATED BY PVRIG LIGATION TO PVRL2

Immunotherapy;Checkpoint Inhibitor;PVRIG;CD112R;Pardoll;PD-1;PD-L1;COM701;Compugen;Cancer;Immunology

Neil, Matthew SPomerantz, Joel ;

Johns Hopkins University

关键词: Immunotherapy;    Checkpoint Inhibitor;    PVRIG;    CD112R;    Pardoll;    PD-1;    PD-L1;    COM701;    Compugen;    Cancer;    Immunology;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/60489/NEIL-THESIS-2018.pdf?sequence=1&isAllowed=n

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

Cancer is a leading public health crisis facing adults in the United States, with estimations that greater than 1.7 million new cancer cases and over 600,000 cancer-related deaths will occur in 2018. While the cost of cancer has continued to increase, therapeutic advances in the treatment of cancer have grown more specific. This specificity has led to decreased toxicity, improved patient tolerance, and increased efficacy. Radiation and chemotherapy are no longer the double-edged swords of the past; fractionated dosage, brachytherapy, and 3-D conformational treatments have made radiotherapy more precise and less toxic. Meanwhile, chemotherapy has undergone its own transformation. The discovery of new types of chemotherapy has expanded physicians’ repertoire for dealing with cancer. Along with surgery, these treatment modalities have proven to be curative for some malignancies.Although cancer-associated mortality rates have dropped by 26% over the past two and a half decades, a large amount of work remains to be accomplished. One avenue that has been explored is through the usage of targeted therapy.Increased understanding of molecular biology has presented the opportunity to tailor treatments to patients. Oncologists can now use monoclonal antibodies (mAb) to individualize therapies to each malignancy. Using mAbs, oncogenic pathways in the tumor microenvironment can be targeted. Immunotherapy represents another treatment modality for oncologists. Immunotherapy leverages the strength of the immune system to destroy malignant cells. The immune system is naturally involved in the defense against cancer. Subsequently, for cancer to progress, it must not only overcome inherent oncolytic cellular processes, but also evade immune surveillance.The goal of immunotherapy is to boost the effectiveness of the immune system in order eliminate cancer cells.The purpose of immune checkpoints is to prohibit an immune response. The aim of checkpoint blockade is to promote immune activation by decreasing suppressive signaling. PD-1 and CTLA-4 were the first two checkpoints targeted. They both have been able to improve outcomes in diseases states that were previously hopeless.Researchers are interested in identifying new checkpoint molecules that could have similar positive effects either individually or in combination. PVRIG is one of these molecules. This protein is expressed on the cell surface of immune cells. It is structurally similar to TIGIT and plays a similar role in regulating immune cell activation. PVRIG, TIGIT, and PD-1 inhibit T-cell activation along the same axis.This paper will review the structure and function of PVRIG. It will focus on its novel role in the immune system and its potential as an immunotherapy. Recent preclinical data will be analyzed, and next steps will be addressed.Advisor: Drew Pardoll MD, PhD