Advances in Immuno-Oncology

**3**

**Chapter 1**

**Abstract**

**1. Introduction**

Immune and Cell Cycle

*Erlinda M. Gordon, Nicole L. Angel, Ted T. Kim,* 

*Don A. Brigham, Sant P. Chawla and Frederick L. Hall*

The rational design of immunotherapeutic agents has advanced with a fundamental understanding that both innate and adaptive immunity play important roles in cancer surveillance and tumor destruction; given that oncogenesis occurs and cancer progresses through the growth of tumor cells with low immunogenicity in an increasingly immunosuppressive tumor microenvironment. Checkpoint inhibitors in the form of monoclonal antibodies that block cancer's ability to deactivate and evade the immune system have been widely indicated for a variety of tumor types. Through targeting the biological mechanisms and pathways that cancer cells use to interact with and suppress the immune system, immunotherapeutic agents have achieved success in inhibiting tumor growth while eliciting lesser toxicities, compared to treatments with standard chemotherapy. Development of "precise" bio-active tumor-targeted gene vectors, biotechnologies, and reagents has also advanced. This chapter presents ongoing clinical research involving immune checkpoint inhibitors, while addressing the clinical potential for tumor-targeted gene blockade in combination with tumor-targeted cytokine delivery, in patients with advanced metastatic disease, providing strategic clinical approaches to precision cancer immunotherapy.

**Keywords:** PD-1 inhibitor, CTLA4 inhibitor, DeltaRex-G, DeltaVax, NK cells,

The human immune system is an intricate network of cell types and signaling pathways that act in a concerted effort to ensure that when an immune response is elicited, it is directly proportional to the severity of the attack. Although this network exists to protect the body from foreign invasion, an overactive immune response can lead to immunopathogenesis and autoimmunity, thus it is crucial that there are mechanisms set in place to ensure this system remains tightly regulated [1]. The immune system achieves this strict regulation by engaging a complex system of checkpoint control pathways. These checkpoints act as metaphorical gateways that require a specific key, in the form of a protein or a small molecule, in order to initiate tightly regulated signaling pathways that prevent over-reactivity of an immune response through the binding of specific cell surface receptors. This process is known as peripheral tolerance [2]. Certain checkpoint pathways,

checkpoint inhibitors, cell cycle control, GMCSF

Immunotherapy

Checkpoint Inhibitors for Cancer
