Our Science and Technology

Problem of “Cold Tumor”

In late years it became clear that the immune system, particularly T cell immunity, can be the powerful weapon for the fight to cancer. T cell-based immunotherapies such as immune checkpoint inhibitors and gene-engineered T cell therapies have been approved. Thus the era of the practical application of cancer immunotherapy began; however the existing immunotherapies are still only effective for the limited population of patients.

Recent preclinical and clinical researches on resistant cancers have revealed that there are two types of cancers: immunologically “hot tumor” and “cold tumor”. Although the existing treatments are effective for hot tumor, it has become clear that they are difficult for cold tumor to work. Hot tumor (or inflamed tumor) is already in immunologically active state where the body’s immune system finds cancer and is fighting against it even before starting treatment. In this type of cancer, immunotherapy is usually effective. Cold tumor (or non-inflamed tumor) is further divided to two classes: immune excluded cold tumor and immune ignored (or desert) cold tumor. In immune excluded cold tumor, the immune system recognizes but cannot affect tumor by various reasons. In immune ignored cold tumor, the immune system has not found tumor at all. In cold tumor, even if the function of anti-tumor immunity is enhanced by immunotherapies, it will not lead to therapeutic effect.

Overcoming the Immune Resistance of Cold Tumor with Combination Immunotherapy using “T-ignite” Anti-Tumor T Cell Activating Technology

Our research team Japan has been working on the discovery of new cancer immunotherapy that can treat cold tumor. By comparing the tumor microenvironment of preclinical murine hot tumor and cold tumor models, the team first found that in cold tumor, tumor-associated macrophages (TAMs) were specifically inactive and did not exert their antigen presentation function, which was assumed as a factor closely related to the immune resistance of cold tumor.

The team then tried to induce antigen presentation function of TAMs using their proprietary anti-tumor T cell activation technology “T-ignite”. As a result, intravenous injection of T-ignite with adjuvant changed the microenvirionment of cold tumor to inflamed status to where anti-tumor T cell could invade. This transformed the cold tumor into hot tumor, making the tumor susceptible to other immunotherapies (patent pending).

In addition, the team also found that subcutaneously injected T-ignite can strongly activate infused tumor-specific T cell receptor (TCR)-engineered T cells, making these cells more powerful to eradicate cold tumor (patent pending).

(Continued to “What is T-ignite?” on the next page)