Partnering with Yisheng

PIKA Technology Platform

PIKA Technology Platform

Multiple Mechanisms of Immune Modulation

PIKA Technology Overview

Yisheng PIKA technology consists of biologic complexes that incorporate an agonist of the TLR3, RIG-I and MDA5 pathways. When delivered with relevant protein-based molecules, PIKA technology can be applied to the development of a new generation of antiviral vaccines, antiviral therapeutics and anticancer therapeutics, offering a promising platform for the development of a wide variety of novel biotherapeutics to improve treatments that are currently available and address unmet medical needs.

PIKA technology is originated from our research in a class of well-defined dsRNA molecules synthesized using our proprietary technology. Endosomal dsRNA can be recognized by TLR3 while cytosolic dsRNA can be sensed by the RIG-I-like receptor family which include RIG-I and MDA-5. Through TLR3, RIG-I and MDA-5 signaling, PIKA technology can induce a prompt production of interferon, cytokines, chemokines and costimulatory factors. The antiviral and antitumor effects of interferon have been well established. Production of type I interferon upon PIKA administration facilitates antigen cross-presentation by dendritic cells and augments CD4+ T-cell, CD8+ T-cell and natural killer-cell responses, which makes PIKA-based therapeutics suitable for both antiviral and antitumor applications.

PIKA Technology: Enabling development of diverse biotherapeutics based on TLR3, RIG-I and MDA5 activation

PIKA Technology: Enabling development of diverse biotherapeutics based on TLR3, RIG-I and MDA5 activation

Multiple Roles of PIKA Technology in the Cancer Immunity Cycle

Effective recognition and removal of cancer cells by the anticancer immune response involves a series of expected events. This sequence of events, which expands with each iteration, is referred to as the cancer-immunity cycle. Yisheng therapeutic candidate YS-ON-001 is able to induce the production of pro-inflammatory cytokines such as interferon alpha, which promote activation of antigen presenting cells (APCs) and enhance antigen presentation (see step 2). YS-ON-001 has demonstrated the ability to upregulate co-stimulatory molecules required for T cell priming and activation (see step 3) such as CD86. In addition, in animal models YS-ON-001 leads to increased infiltration of T cells and NK cells into tumors (see step 5).

PIKA Technology: Enabling the disruption of tumor growth in multiple steps of the cancer-immunity cycle

PIKA Technology: Enabling the disruption of tumor growth in multiple steps of immunotherapy

Immune Cell Types Involved in the Antitumor Immune Response

YS-ON-001 has been found to increase the relative number of T cells and NK cells in the tumor microenvironment, convert tumor-associated macrophages from the pro-tumorigenic M2 macrophage subtype to the anti-tumorigenic M1 macrophage subtype. YS-ON-001 also decreases the number of regulatory T cells and myeloid-derived suppressor cells, reducing the suppressive effects of regulatory T cells and myeloid-derived suppressor cells on effector immune cells. The dual effects lead to efficient killing of cancer cells (see step 7). The effects of YS-ON-001 on immunomodulating and anti-neoplastic activities at multiple stages of the cancer immunity cycle make YS-ON-001 an attractive therapeutic candidate when developed either as a standalone therapy or when used in combination with other therapeutic modalities.

PIKA Technology: Enabling the activation of antitumor cell activity and the reduction of immunosuppressive effects of specific immune cells

PIKA Technology: Enabling the activation of antitumor cell activity and the reduction of immunosuppressive effects of specific immune cells