Making Tumors Visible to the Immune System

The immune system has the ability to eliminate cancer cells, and immunotherapies work by helping it recognize and attack tumors more effectively.

For immune cells to identify and destroy cancer cells, tumor-derived antigens must be displayed on the cell surface through the HLA-I (MHC class I) antigen presentation pathway. This process is essential for enabling T cells to distinguish abnormal cells from healthy tissue. Many cancers evade immune attack by suppressing this antigen presentation machinery. They reduce HLA-I expression, impair antigen processing, and disrupt antigen presentation, effectively rendering tumor cells “invisible” to the immune system.

As a result, even in tumors with abundant immune cell infiltration, patients may fail to respond to immunotherapy due to immune evasion.

Long non-coding RNAs (lncRNAs) are RNA molecules that do not encode proteins but regulate gene expression and cellular programs. They represent one of the largest and least-characterized classes of the human genome, with thousands still functionally unannotated.Increasing evidence suggests that specific lncRNAs play key roles in cancer progression and immune regulation, including pathways involved in immune suppression and treatment resistance.

Because they are often highly cell- and context-specific, lncRNAs represent a promising but largely untapped class of therapeutic targets. LncRNAs can show restricted expression in specific tumor types or disease states, creating an opportunity for more selective therapeutic intervention with reduced impact on healthy tissues.

ONC-1929 is Oncolinc’s lead oligonucleotide therapeutic candidate designed to selectively target a novel immunosuppressive long non-coding RNA implicated in tumor progression and immune evasion.

ONC-1929 is designed to restore tumor immune visibility and re-engage anti-tumor T cell responses. In preclinical studies, ONC-1929 has demonstrated the potential to enhance T cell-mediated cytotoxicity and improve responses to immune checkpoint blockade.

As a first-in-class lncRNA-targeted immunotherapy, ONC-1929 represents a new approach to overcoming tumor immune resistance.