Oncternal is developing a ROR-1 targeted CAR-T therapy, which is currently in preclinical development at UC San Diego for hematologic and solid tumors, with funding from the California Institute for Regenerative Medicine (CIRM).
ROR1 is an Attractive Target for CAR-T Therapy
Chimeric antigen receptor T-cell (CAR-T) therapies are T cells that have been engineered to target and engage a specific marker on cancer cells in an effort to direct an immune response against those cancer cells. CAR-T therapies have shown dramatic effects as treatments of CD19-expressing leukemias and lymphomas and BCMA-expressing myeloma.
ROR1 is highly expressed on many solid and hematologic cancers but not often expressed on healthy tissue. Importantly, ROR1 expression confers a survival advantage to the tumor cells, making ROR1 negative relapses less likely. Our first generation ROR1 CAR-T specifically lysed ROR1+ target cells and inhibited ROR1+ tumors in vivo. We are currently optimizing a second generation construct with a cirmtuzumab-based ScFv.
Unmet Medical Need for CAR-T Therapies
Remarkable clinical responses have been observed in patients treated with CAR-T therapy, but at a cost of considerable toxicity including cytokine release syndrome and neurologic toxicity, both of which can be severe and sometimes fatal. A CAR-T treatment that is not activated by normal cells expressing the target antigen might reduce some of these toxicities. Patients who have responded to CAR-T therapy are sometimes experiencing relapses of their cancer with a mutated or absent target tumor antigen (such as CD19). Targeting the CAR-T to a tumor antigen that is important to the cancer cell’s survival or aggressiveness might offer a decreased likelihood of antigen negative relapses developing.
We are enrolling patients:
- With B-Cell Lymphoid Malignancies (chronic lymphocytic leukemia and mantle cell lymphoma) for a Phase 1b/2 study of cirmtuzumab in combination with ibrutinib
- With HER2 negative, metastatic breast cancer for a Phase 1b study of cirmtuzumab in combination with paclitaxel
- With relapsed/refractory CLL for a Phase 2 clinical study of cirmtuzumab in combination with venetoclax, a Bcl-2 inhibitor
- With Ewing sarcoma for a Phase 1 study of TK216, our small-molecule inhibitor of ETS-family transcription factor oncoproteins, in combination with vincristine