A cancer vaccine trains a patient’s immune system to identify and destroy cancer cells.

• A cancer vaccine works by:
  • Identifying markers that distinguish tumor cells from normal cells.
  • Displaying these markers on the surface of antigen-presenting cells (APC).
  • Using this presentation to train T cells to recognize and kill cancer cells.
• We are developing an mRNA-based vaccine (similar to the COVID vaccine) that instructs APC to make and present selected tumor markers.
  • We are employing various immune monitoring approaches to characterize the immune system’s response to these vaccines to inform future vaccine development.
  • We include neoantigen markers caused by 2 types of tumor-specific mutations:
    • Single-nucleotide variant (SNV): a changed base at a single location of the DNA
    • Structural variant (SV): a stretch of changed bases in the DNA from larger disruptions like chromosomal rearrangements
• How we are contributing to the field:
  • We funded the development of new algorithms to identify neoantigens arising from structural variants (SV), which are large-scale chromosomal rearrangements that were previously underused as vaccine targets.
  • We pioneered the first-in-human vaccine built from these SV-derived neoantigens.
  • We are building on an mRNA-based platform, the same technology as the COVID-19 vaccines, to enable rapid, personalized manufacturing tailored to each patient's tumor.

Chimeric Antigen Receptor (CAR) T-cell therapy engineers T cells to kill cancer cells with certain cell-surface markers.

• CAR-Ts have transformed the treatment of some blood cancers [1], but their efficacy has been much less in solid cancers.
• To make CAR-T effective for solid cancers, they need to be more potent and durable.
• However, enhancing CAR-T could lead to side effects (toxicity), if the markers that the CAR-T is going after is also present in sufficient quantities in healthy cells.
• To overcome this, we're developing a logic-gated CAR-T using a system called SyNthetic Intramembrane Proteolysis Receptors (SNIPR) [2], that uses a two-step process to improve the specificity.
  • The SNIPR recognizes a first marker in the cancer cell that triggers the production of a CAR.
  • The CAR recognizes a different second target for killing.
  • Only cancer cells that express the CAR target and are close to cells expressing the SNIPR targets should be killed.
• We are currently developing the first version of this construct that targets HER2 and DLK1.

We are also actively exploring and seeking collaborations with experts in the following areas:

• Radioligand therapy: Using alpha- or beta-emitters to deliver targeted radiation directly to cancer cells.
• PROTAC and molecular glue degraders: Small molecules that act as "protein degraders" to remove specific intracellular protein targets.
• siRNA: Using small interfering RNA to silence the expression of specific gene targets.