Stephanie K. Dougan, PhD, assistant professor, microbiology and immunobiology, Division of Immunology, Harvard Medical School, researcher, Dana-Farber Cancer Institute, discusses ways to extend the promise of immunotherapy to the field of pancreatic cancer.

Patients with pancreatic cancer have a very poor prognosis overall, explains Dougan. The disease becomes metastatic very quickly, which has translated to a 5-year survival rate of under 10%. The current standard of care is combination chemotherapy—–either gemcitabine and paclitaxel or FOLFIRINOX. However, neither of these regimens translate to a significant extension in survival, says Dougan.

Research has turned toward immunotherapy as a way to improve survival for patients. Notably, in December 2018, the combination of the CXCR4 antagonist BL-8040 and the PD-1 inhibitor pembrolizumab (Keytruda) showed encouraging survival data in a phase IIa trial of patients with metastatic pancreatic adenocarcinoma (NCT02826486). Data reported at the 2018 ESMO Congress revealed a median overall survival of 3.4 months, and 7.5 months for those who had received at least 1 prior line of therapy.

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Extending the Promise of Immunotherapy to Pancreatic Cancer

Stephanie K. Dougan, PhD, assistant professor, Microbiology and Immunobiology, Division of Immunology, Harvard Medical School, researcher, Dana-Farber Cancer Institute, discusses ways of augmenting T-cell immunity in pancreatic cancer.

The current standard of care for patients with pancreatic cancer is combination chemotherapy, such as FOLFIRINOX or gemcitabine and nab-paclitaxel (Abraxane). However, the prognosis remains poor, notes Dougan. Though immunotherapy has been examined in the space, it has not seen much success, prompting investigators to examine ways to augment T-cell priming. Checkpoint blockade operates by de-inhibiting T cells, thereby taking the breaks off the immune system. The contingency with this approach is that the patient has T cells to begin with, which is not true of all malignancies, says Dougan.

Dougan and her fellow investigators have found that activating a small molecule can induce noncanonical NF-kB2 signaling. By augmenting co-stimulation through TNF family receptors, T cells are given a signal. This ultimately enables the priming of T cells that harbor less abundant antigens, states Dougan.

Stephanie K. Dougan, PhD

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Extending the Promise of Immunotherapy to Pancreatic Cancer

Augmenting T-Cell Immunity in Pancreatic Cancer