Background

In the field of oncology, Chimeric Antigen Receptor T-cell (CAR-T) therapy has demonstrated remarkable success in treating hematological malignancies such as leukemia and multiple myeloma, establishing itself as a cornerstone of cancer immunotherapy. However, its efficacy has been limited in solid tumors, including gastric cancer, colorectal cancer, and lung cancer.

One of the primary reasons for this limitation is the difficulty in identifying tumor-specific antigens that can selectively target solid tumor cells. Many antigens expressed by cancer cells are also partially expressed in normal cells, which poses a risk of CAR-T cells attacking normal tissues and causing severe side effects. Furthermore, the heterogeneity within tumors, where not all cancer cells express the same antigen, can also lead to treatment failure.

The tumor microenvironment (TME) surrounding solid tumors also presents a significant barrier. The TME secretes various immunosuppressive substances that inhibit the infiltration and activity of CAR-T cells. Previous research efforts have focused on discovering new target antigens for solid tumors or combining immune checkpoint inhibitors to address this issue, but these approaches have not been entirely successful in overcoming the robust defenses of solid tumors.

Key Findings

Dispatch Bio, a U.S.-based biotechnology company, has developed Flare, a technology platform that utilizes oncolytic viruses (OVs) to overcome these limitations. The Flare platform takes a different approach by inducing the expression of artificial target antigens on the surface of cancer cells using viruses, rather than targeting naturally occurring antigens present in cancer cells.

Dispatch Bio designed a recombinant oncolytic virus, DV-10, and initially administered it to solid tumor cells. DV-10 penetrates and replicates within the cancer cells, leading to the concentrated expression of a modified B-cell maturation antigen (dBCMA) on the surface of the solid tumor cells. This causes the solid tumor cells to mimic the appearance of multiple myeloma cells. Subsequently, when patients are administered existing CAR-T therapies that target BCMA, the CAR-T cells recognize the solid tumor cells as hematological cancer cells and initiate targeted destruction.

DV-10 is more than just an antigen delivery vehicle. The virus is genetically engineered to release immune-activating factors, such as interleukin-18 (IL-18), and T-cell-attracting chemokines, such as CXCL9. These substances reprogram the TME, which is typically immunosuppressive, into an active state, facilitating the infiltration of CAR-T cells into the tumor core. By simultaneously controlling the introduction of artificial antigens and the modification of the microenvironment, the Flare platform enhances the efficacy of solid tumor treatment.

To validate the efficacy of the Flare platform, Dispatch Bio received approval for a Phase 1 clinical trial (DISP-10) combining Bristol Myers Squibb (BMS)'s BCMA-targeted CAR-T therapy, idecabtagene vicleucel (ide-cel), with DV-10. As of August 2026, the trial has completed enrollment of patients with advanced gastrointestinal cancers, and the pipeline is being expedited through the Fast Track designation by the U.S. Food and Drug Administration (FDA). In addition, a Phase 1 clinical trial (DISP-11) combining DV-10 with CARsgen Therapeutics' BCMA-targeted CAR-T therapy, zevorcabtagene autoleucel (zev-cel), is also underway, demonstrating the platform's potential for broad applicability.

Significance and Prospects

The Flare platform opens up new possibilities for expanding the use of existing CAR-T therapies, originally developed for hematological malignancies, to solid tumors. Instead of developing new CAR-T therapies specifically for solid tumors from scratch, the platform allows for the use of existing, safe, and effective BCMA-targeted CAR-T therapies, which can shorten the development time and reduce the cost associated with developing new CAR-T therapies. This approach represents a significant advancement in the field of solid tumor drug development.

However, there are still challenges to be addressed before the technology can be commercialized. A key factor is the extent to which the DV-10 virus can uniformly and efficiently express artificial antigens in solid tumor tissues. If the antigen is only expressed in a subset of cancer cells, the remaining cancer cells may survive, leading to tumor recurrence. The potential for immune rejection of the virus or the formation of neutralizing antibodies against the virus after repeated administrations also needs to be addressed.

The researchers are closely monitoring the performance of the virus in the complex tumor microenvironment of actual patients, beyond the animal model level, to ensure that it functions as designed. The safety and efficacy data from this Phase 1 clinical trial will be critical in determining the future success of this technology.